Is DYSF p.Asp380Val (c.1139A>T) pathogenic?

DYSF p.Asp380Val (c.1139A>T) is classified Uncertain significance in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely pathogenic (0.8463); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DYSF p.Asp380Val (c.1139A>T)?

DYSF p.Asp380Val (c.1139A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DYSF p.Asp380Val (c.1139A>T) in the general population?

DYSF p.Asp380Val (c.1139A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYSF p.Asp380Val (c.1139A>T)?

AlphaMissense predicts likely pathogenic (score 0.8463) — an in-silico prediction, not a clinical call.

DYSF p.Asp380Val

c.1139A>T · VCV4245961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8463 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8463	likely pathogenic
REVEL	0.864	moderately pathogenic-leaning
SaProt	LLR -10.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 85 kb · p 0.54 · regional, not allelic
Overall
CADD	23.5	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 D348V vs ClinVar D380V) — 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.Asp380Val
Coding: c.1139A>T
MANE Select: NM_001130987
Type: single nucleotide variant
Location: chr2:71520894 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 380: a β-strand; the c2 3 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

Similar variants

DYSF p.Asp380= 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-asp380val (accessed [today's date]).

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