Is DYSF p.Asn994= (c.2982C>T) pathogenic?

DYSF p.Asn994= (c.2982C>T) is classified Conflicting classifications of pathogenicity in DYSF (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-26). Rare (popmax 0.329%, afr); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

What condition is associated with DYSF p.Asn994= (c.2982C>T)?

DYSF p.Asn994= (c.2982C>T) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin, autosomal recessive limb-girdle muscular dystrophy type 2B, Miyoshi muscular dystrophy 1 (ClinVar).

How common is DYSF p.Asn994= (c.2982C>T) in the general population?

DYSF p.Asn994= (c.2982C>T) is rare (popmax 0.329%, afr) (gnomAD).

DYSF p.Asn994=

c.2982C>T · rs142404822 · VCV499191

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.329%, afr)

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.72 · evaluated, not missing
Constraint at this position
Conservation	phyloP -13	GERP -4.3
Overall
CADD	0.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.329% African / African-American · 247/75,004 alleles

Filtering AF 0.296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.282%

Overall 0.0192% 310/1,613,892 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.329%	304
Middle Eastern	0.033%	3,031
Admixed American	0.0283%	3,530
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Finnishnot grpmax-eligible	0.00625%	16,004
European (non-Finnish)	0.00229%	43,698

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.Asn994=
Coding: c.2982C>T
MANE Select: NM_001130987
dbSNP: rs142404822
Type: single nucleotide variant
Location: chr2:71570231 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 994: a β-strand

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 Miyoshi muscular dystrophy 1

Similar variants

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
DYSF c.1276+5G>C 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-asn994 (accessed [today's date]).

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