Is DYSF p.Phe1829Ser (c.5486T>C) pathogenic?

DYSF p.Phe1829Ser (c.5486T>C) is classified Uncertain significance in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-21). AlphaMissense: likely pathogenic (0.9681); Absent from gnomAD v4.1; Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Phe1829Ser (c.5486T>C) in the general population?

DYSF p.Phe1829Ser (c.5486T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYSF p.Phe1829Ser (c.5486T>C)?

AlphaMissense predicts likely pathogenic (score 0.9681) — an in-silico prediction, not a clinical call.

DYSF p.Phe1829Ser

Q: What condition is associated with DYSF p.Phe1829Ser (c.5486T>C)?

DYSF p.Phe1829Ser (c.5486T>C) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.5486T>C · rs2546571025 · VCV1717415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9681 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Computational evidence

Protein change
AlphaMissense	0.9681	likely pathogenic · top 8% in DYSF
REVEL	0.914	moderately pathogenic-leaning
SaProt	LLR -13.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 F1790S vs ClinVar F1829S) — 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.Phe1829Ser
Coding: c.5486T>C
MANE Select: NM_001130987
dbSNP: rs2546571025
Type: single nucleotide variant
Location: chr2:71668782 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1790 UniProt numbering: 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

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+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-phe1829ser (accessed [today's date]).

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