Is DYSF p.Val2004Met (c.6010G>A) pathogenic?

DYSF p.Val2004Met (c.6010G>A) is classified Uncertain significance in DYSF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-25). AlphaMissense: likely benign (0.1627); Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy type 2B.

What condition is associated with DYSF p.Val2004Met (c.6010G>A)?

DYSF p.Val2004Met (c.6010G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2B (ClinVar).

How common is DYSF p.Val2004Met (c.6010G>A) in the general population?

DYSF p.Val2004Met (c.6010G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYSF p.Val2004Met (c.6010G>A)?

AlphaMissense predicts likely benign (score 0.1627) — an in-silico prediction, not a clinical call.

DYSF p.Val2004Met

Q: How is Dysferlin-related limb-girdle muscular dystrophy R2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.6010G>A · VCV4067032

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1627 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2B

Computational evidence

Protein change
AlphaMissense	0.1627	likely benign
REVEL	0.464	indeterminate
SaProt	LLR -7.42	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 4.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	23.3	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 V1965M vs ClinVar V2004M) — 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.Val2004Met
Coding: c.6010G>A
MANE Select: NM_001130987
Type: single nucleotide variant
Location: chr2:71679182 (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 type 2B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dysferlin-related limb-girdle muscular dystrophy R2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult
Prevalence: 1-9 / 1 000 000 (United Kingdom)

Similar variants

DYSF p.Val2004= Likely benign ★ same residue
DYSF c.1033+1G>A 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
DYSF c.1481-1G>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-val2004met (accessed [today's date]).

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