Is DYSF p.Asp744Val (c.2231A>T) pathogenic?

DYSF p.Asp744Val (c.2231A>T) is classified Likely benign in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-21). AlphaMissense: likely benign (0.134); Ultra-rare (popmax 0.0107%, afr); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Asp744Val (c.2231A>T) in the general population?

DYSF p.Asp744Val (c.2231A>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about DYSF p.Asp744Val (c.2231A>T)?

AlphaMissense predicts likely benign (score 0.134) — an in-silico prediction, not a clinical call.

DYSF p.Asp744Val

Q: What condition is associated with DYSF p.Asp744Val (c.2231A>T)?

DYSF p.Asp744Val (c.2231A>T) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.2231A>T · rs552533697 · VCV2917730

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.134 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Computational evidence

Protein change
AlphaMissense	0.134	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -10.39	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.67, phastCons 0.049
Regional constraint	o/e 0.82	unconstrained · MANE · 18 kb · p 4.1e-05 · regional, not allelic
Overall
CADD	18.16	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 D726V vs ClinVar D744V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/75,014 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000496% 8/1,614,094 alleles · ultra-rare exomes 5/1,461,886 · genomes 3/152,208 · joint denominator

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.Asp744Val
Coding: c.2231A>T
MANE Select: NM_001130987
dbSNP: rs552533697
Type: single nucleotide variant
Location: chr2:71561766 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 726 UniProt numbering: an α-helix

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

Similar variants

DYSF p.Asp744= Likely 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+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-asp744val (accessed [today's date]).

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