Is DYSF p.Ser1147Phe (c.3440C>T) pathogenic?

DYSF p.Ser1147Phe (c.3440C>T) is classified Conflicting classifications of pathogenicity in DYSF (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-03). AlphaMissense: likely benign (0.1786); Ultra-rare (popmax 0.0439%, sas); Associated with Inborn genetic diseases.

What condition is associated with DYSF p.Ser1147Phe (c.3440C>T)?

DYSF p.Ser1147Phe (c.3440C>T) is associated with Inborn genetic diseases, neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

How common is DYSF p.Ser1147Phe (c.3440C>T) in the general population?

DYSF p.Ser1147Phe (c.3440C>T) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

What do computational predictors say about DYSF p.Ser1147Phe (c.3440C>T)?

AlphaMissense predicts likely benign (score 0.1786) — an in-silico prediction, not a clinical call.

DYSF p.Ser1147Phe

c.3440C>T · rs755476936 · VCV2143048

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1786 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1786	likely benign
REVEL	0.48	indeterminate
SaProt	LLR -11.06	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	23.4	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 S1129F vs ClinVar S1147F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0439% South Asian · 40/91,082 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00254% 41/1,613,978 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Ser1147Phe
Coding: c.3440C>T
MANE Select: NM_001130987
dbSNP: rs755476936
Type: single nucleotide variant
Location: chr2:71589630 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1147: a β-strand; the c2 4 domain

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.Ser1147= 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-ser1147phe (accessed [today's date]).

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