Is DYSF p.Ser725Trp (c.2174C>G) pathogenic?

DYSF p.Ser725Trp (c.2174C>G) is classified Uncertain significance in DYSF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-11-22). AlphaMissense: likely benign (0.1648); Absent from gnomAD v4.1.

How common is DYSF p.Ser725Trp (c.2174C>G) in the general population?

DYSF p.Ser725Trp (c.2174C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYSF p.Ser725Trp (c.2174C>G)?

AlphaMissense predicts likely benign (score 0.1648) — an in-silico prediction, not a clinical call.

DYSF p.Ser725Trp

c.2174C>G · rs376571932 · VCV597360

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1648 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,578,818)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1648	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -10.22	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 2.8	GERP 0.46, phastCons 0.4
Regional constraint	o/e 0.82	unconstrained · MANE · 18 kb · p 4.1e-05 · regional, not allelic
Overall
CADD	21.0	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 S707W vs ClinVar S725W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,578,818). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DYSF
Protein: p.Ser725Trp
Coding: c.2174C>G
MANE Select: NM_001130987
dbSNP: rs376571932
Type: single nucleotide variant
Location: chr2:71556029 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 725: an α-helix

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

Similar variants

DYSF p.Ser725= Conflicting classifications of pathogenicity ★ same residue
DYSF p.Ser725Thr Uncertain significance ★ ⚠ same residue
DYSF c.1003-3C>A Pathogenic ★★★ same type
DYSF c.1033+1G>A Pathogenic ★★★ same type
DYSF c.1033+4A>T Likely pathogenic ★★★ same type
DYSF c.1033+5G>A Likely pathogenic ★★★ same type
DYSF c.1149+1G>A Pathogenic ★★★ same type
DYSF c.1149+1G>C Pathogenic ★★★ same type

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-ser725trp (accessed [today's date]).

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