Is DYSF p.Cys1724Ser (c.5171G>C) pathogenic?

DYSF p.Cys1724Ser (c.5171G>C) is classified Uncertain significance in DYSF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-07). AlphaMissense: ambiguous (0.4813); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with DYSF p.Cys1724Ser (c.5171G>C)?

DYSF p.Cys1724Ser (c.5171G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DYSF p.Cys1724Ser (c.5171G>C) in the general population?

DYSF p.Cys1724Ser (c.5171G>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DYSF p.Cys1724Ser (c.5171G>C)?

AlphaMissense predicts ambiguous (score 0.4813) — an in-silico prediction, not a clinical call.

DYSF p.Cys1724Ser

c.5171G>C · rs777984362 · VCV1806853

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4813 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4813	ambiguous
REVEL	0.479	indeterminate
SaProt	LLR -4.70	tolerated
Splicing
SpliceAI	Δ0.75	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.9	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	24.7	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 C1685S vs ClinVar C1724S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000205% 3/1,461,812 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,442
South Asian	0.0011%	91,078

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.Cys1724Ser
Coding: c.5171G>C
MANE Select: NM_001130987
dbSNP: rs777984362
Type: single nucleotide variant
Location: chr2:71664435 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYSF p.Cys1724Phe Uncertain significance ★ ⚠ same residue
DYSF p.Cys1724Tyr Uncertain significance ★ ⚠ same residue
DYSF p.Ala1024Pro Uncertain significance ★★ ⚠ same condition
DYSF p.Ala736Thr Uncertain significance ★★ ⚠ same condition
DYSF p.Ala829Val Uncertain significance ★★ ⚠ same condition
DYSF p.Arg1062His Uncertain significance ★★ ⚠ same condition
DYSF p.Arg1102Leu Uncertain significance ★★ ⚠ same condition
DYSF p.Arg1111Cys Uncertain significance ★★ ⚠ 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-cys1724ser (accessed [today's date]).

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