Is DYSF p.Ala382Val (c.1145C>T) pathogenic?

DYSF p.Ala382Val (c.1145C>T) is classified Benign/Likely benign in DYSF (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1533); Low-frequency (popmax 1.18%, afr); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Ala382Val (c.1145C>T) in the general population?

DYSF p.Ala382Val (c.1145C>T) is low-frequency (popmax 1.18%, afr) (gnomAD).

What do computational predictors say about DYSF p.Ala382Val (c.1145C>T)?

AlphaMissense predicts likely benign (score 0.1533) — an in-silico prediction, not a clinical call.

DYSF p.Ala382Val

Q: What condition is associated with DYSF p.Ala382Val (c.1145C>T)?

DYSF p.Ala382Val (c.1145C>T) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin, autosomal recessive limb-girdle muscular dystrophy type 2B (ClinVar).

c.1145C>T · rs115279465 · VCV282164

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1533 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.18%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Computational evidence

Protein change
AlphaMissense	0.1533	likely benign
REVEL	0.352	indeterminate
SaProt	LLR -4.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 85 kb · p 0.54 · regional, not allelic
Overall
CADD	23.9	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 A350V vs ClinVar A382V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.18% African / African-American · 886/75,014 alleles

Filtering AF 1.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.09%

Overall 0.0709% 1,144/1,613,988 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.18%	85
East Asian	0.236%	423
Remaining individualsnot grpmax-eligible	0.0736%	1,359
Admixed American	0.0666%	1,501
Middle Eastern	0.0498%	2,010
European (non-Finnish)	0.00517%	19,343
Finnishnot grpmax-eligible	0.00156%	64,014
South Asian	0.0011%	91,084

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.Ala382Val
Coding: c.1145C>T
MANE Select: NM_001130987
dbSNP: rs115279465
Type: single nucleotide variant
Location: chr2:71520900 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 382: a β-strand; the c2 3 domain

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

Disease context

neuromuscular disease caused by qualitative or quantitative defects of dysferlin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2B

Similar variants

DYSF p.Ala382= Benign ★ same residue
DYSF c.1003-3C>A Pathogenic ★★★ same condition
DYSF c.1033+1G>A Pathogenic ★★★ same condition
DYSF c.1033+4A>T 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.1276+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-ala382val (accessed [today's date]).

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