Is DYSF p.Ala801Val (c.2402C>T) pathogenic?

DYSF p.Ala801Val (c.2402C>T) is classified Likely benign in DYSF (ClinVar, Expert panel, 7 submitters; last evaluated 2026-01-23). AlphaMissense: likely benign (0.1916); Rare (popmax 0.164%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy.

What condition is associated with DYSF p.Ala801Val (c.2402C>T)?

DYSF p.Ala801Val (c.2402C>T) is associated with autosomal recessive limb-girdle muscular dystrophy, autosomal recessive limb-girdle muscular dystrophy type 2B, Miyoshi myopathy (ClinVar).

How common is DYSF p.Ala801Val (c.2402C>T) in the general population?

DYSF p.Ala801Val (c.2402C>T) is rare (popmax 0.164%, afr) (gnomAD).

What do computational predictors say about DYSF p.Ala801Val (c.2402C>T)?

AlphaMissense predicts likely benign (score 0.1916) — an in-silico prediction, not a clinical call.

DYSF p.Ala801Val

c.2402C>T · rs147139414 · VCV288008

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1916 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.164%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive limb-girdle muscular dystrophy

ClinGen expert panel — Limb Girdle Muscular Dystrophy VCEP

Likely Benign for autosomal recessive limb-girdle muscular dystrophy. Applied ACMG criteria (verbatim):

BS1

Curation rationale (ClinGen, verbatim)

The NM_003494.4: c.2348C>T variant in DYSF, which is also known as NM_001130987.2: c.2402C>T p.(Ala801Val), is a missense variant predicted to cause substitution of alanine to valine at amino acid 801, p.(Ala801Val). This variant has been observed in at least three individuals with suspected LGMD in a heterozygous state, but none of them would be scoreable for PM3 application (PMID: 30564623, Jain Foundation Dysferlin Registry internal data communication; PM3_supporting not met). The filtering allele frequency of this variant is 0.001406 (the lower threshold of the 95% CI of 123/74924 African/African American chromosomes) in gnomAD v4.1.0, which is greater than the LGMD VCEP BS1 threshold (>0.001) (BS1 met). The computational predictor REVEL gives a score of 0.28 (PP3 and BP4 not met). In summary, this variant is classified as likely benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (specifications v2.0.0; 01/23/2026): BS1.

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
AlphaMissense	0.1916	likely benign
REVEL	0.381	indeterminate
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 18 kb · p 4.1e-05 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A783V vs ClinVar A801V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.164% African / African-American · 123/74,924 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.0093% 150/1,613,614 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.164%	609
Admixed American	0.025%	3,998
Remaining individualsnot grpmax-eligible	0.0176%	5,678
South Asian	0.0011%	90,992

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DYSF
Protein: p.Ala801Val
Coding: c.2402C>T
MANE Select: NM_001130987
dbSNP: rs147139414
Type: single nucleotide variant
Location: chr2:71561937 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB

Full DYSF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2B Miyoshi myopathy distal myopathy with anterior tibial onset neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Similar variants

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DYSF c.1033+4A>T Likely pathogenic ★★★ same condition
DYSF c.1033+5G>A Likely pathogenic ★★★ same condition
DYSF c.1149+1G>A Pathogenic ★★★ same condition
DYSF c.1149+1G>C Pathogenic ★★★ same condition
DYSF c.1149+4A>G Pathogenic ★★★ same condition
DYSF c.1149+5G>A Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dysf-p-ala801val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown