Is DYSF p.Ala829Val (c.2486C>T) pathogenic?

DYSF p.Ala829Val (c.2486C>T) is classified Uncertain significance in DYSF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-10). AlphaMissense: likely benign (0.1456); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DYSF p.Ala829Val (c.2486C>T)?

DYSF p.Ala829Val (c.2486C>T) is associated with Inborn genetic diseases, neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

How common is DYSF p.Ala829Val (c.2486C>T) in the general population?

DYSF p.Ala829Val (c.2486C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYSF p.Ala829Val (c.2486C>T)?

AlphaMissense predicts likely benign (score 0.1456) — an in-silico prediction, not a clinical call.

DYSF p.Ala829Val

c.2486C>T · rs2091948098 · VCV1016489

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1456 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1456	likely benign
REVEL	0.514	indeterminate
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.3, phastCons 0.98
Regional constraint	o/e 0.82	unconstrained · MANE · 18 kb · p 4.1e-05 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A811V vs ClinVar A829V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DYSF
Protein: p.Ala829Val
Coding: c.2486C>T
MANE Select: NM_001130987
dbSNP: rs2091948098
Type: single nucleotide variant
Location: chr2:71564134 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 829: a turn

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Similar variants

DYSF p.Ala829= Likely benign ★★ same residue
DYSF p.Ala829Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
DYSF p.Ala829fs Pathogenic ★ same residue
DYSF p.Ala829Ser Uncertain significance ★ ⚠ 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

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-ala829val (accessed [today's date]).

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