Is DYSF p.Pro979Ser (c.2935C>T) pathogenic?

DYSF p.Pro979Ser (c.2935C>T) is classified Uncertain significance in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely pathogenic (0.7482); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DYSF p.Pro979Ser (c.2935C>T)?

DYSF p.Pro979Ser (c.2935C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DYSF p.Pro979Ser (c.2935C>T) in the general population?

DYSF p.Pro979Ser (c.2935C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DYSF p.Pro979Ser (c.2935C>T)?

AlphaMissense predicts likely pathogenic (score 0.7482) — an in-silico prediction, not a clinical call.

DYSF p.Pro979Ser

c.2935C>T · VCV4015743

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7482 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7482	likely pathogenic
REVEL	0.711	pathogenic-leaning
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 18 kb · p 4.1e-05 · regional, not allelic
Overall
CADD	24.5	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 P961S vs ClinVar P979S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.2e-05% 1/1,614,140 alleles · very rare exomes 1/1,461,828 · genomes 0/152,312 · joint denominator

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.Pro979Ser
Coding: c.2935C>T
MANE Select: NM_001130987
Type: single nucleotide variant
Location: chr2:71569890 (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.Pro979= Conflicting classifications of pathogenicity ★ 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
DYSF p.Arg1169His 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-pro979ser (accessed [today's date]).

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