Is DYSF p.Ser1711Phe (c.5132C>T) pathogenic?

DYSF p.Ser1711Phe (c.5132C>T) is classified Likely pathogenic in DYSF (ClinVar, Expert panel, 3 submitters; last evaluated 2026-03-23). AlphaMissense: likely pathogenic (0.9757); Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy.

What condition is associated with DYSF p.Ser1711Phe (c.5132C>T)?

DYSF p.Ser1711Phe (c.5132C>T) is associated with autosomal recessive limb-girdle muscular dystrophy, neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

How common is DYSF p.Ser1711Phe (c.5132C>T) in the general population?

DYSF p.Ser1711Phe (c.5132C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYSF p.Ser1711Phe (c.5132C>T)?

AlphaMissense predicts likely pathogenic (score 0.9757) — an in-silico prediction, not a clinical call.

DYSF p.Ser1711Phe

c.5132C>T · VCV3677022

Likely pathogenic Expert panel

Classification

Likely pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9757 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive limb-girdle muscular dystrophy

ClinGen expert panel — Limb Girdle Muscular Dystrophy VCEP

Likely Pathogenic for autosomal recessive limb-girdle muscular dystrophy. Applied ACMG criteria (verbatim):

PM2_Supporting PP4_Strong PM3

Curation rationale (ClinGen, verbatim)

The NM_003494.4: c.5015C>T variant in DYSF, which is also known as NM_001130987.2: c.5132C>T p.(Ser1711Phe), is a missense variant predicted to cause substitution of serine to phenylalanine at amino acid 1672, p.(Ser1672Phe). This variant has been reported in at least two patients with features consistent with LGMD (PMID: 33927379, 32528171; LOVD DYSF_001234), where it was identified in unconfirmed phase with a pathogenic variant in both (NM_003494.4: c.797G>A (p.Gly266Glu), 0.5 pts, MYO-SEQ internal data communication, PMID: 32528171; c.799_800del p.(Phe267LeufsTer5), 0.5 pts, PMID: 33927379, LOVD Individuals #00327046 and #0032760) (PM3). At least one of these individuals displayed progressive limb girdle muscle weakness and absent dysferlin on muscle biopsy (PMID: 32528171, MYO-SEQ internal data communication; PP4_Strong). This variant is absent from gnomAD v.4.1.0, meeting the criteria for PM2_Supporting. The computational predictor REVEL gives a score of 0.592, which is below the LGMD VCEP threshold of ≥0.70 (PP3 not met). In summary, this variant meets the criteria to be classified as Likely pathogenic for autosomal recessive limb-girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 2.0.0; 03/23/2026): PM3, PP4_Strong, PM2_Supporting.

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
AlphaMissense	0.9757	likely pathogenic ✓ concordant with ClinVar · top 7% in DYSF
REVEL	0.592	indeterminate
SaProt	LLR -14.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	26.5	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 S1672F vs ClinVar S1711F) — 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.Ser1711Phe
Coding: c.5132C>T
MANE Select: NM_001130987
Type: single nucleotide variant
Location: chr2:71664396 (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 — 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 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.1033+5G>A 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.1149+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-ser1711phe (accessed [today's date]).

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