Is DYSF p.Pro804His (c.2411C>A) pathogenic?

DYSF p.Pro804His (c.2411C>A) is classified Uncertain significance in DYSF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-26). AlphaMissense: likely pathogenic (0.7408); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DYSF p.Pro804His (c.2411C>A)?

DYSF p.Pro804His (c.2411C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DYSF p.Pro804His (c.2411C>A) in the general population?

DYSF p.Pro804His (c.2411C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYSF p.Pro804His (c.2411C>A)?

AlphaMissense predicts likely pathogenic (score 0.7408) — an in-silico prediction, not a clinical call.

DYSF p.Pro804His

c.2411C>A · rs768226528 · VCV290608

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7408 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7408	likely pathogenic
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -6.39	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 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 18 kb · p 4.1e-05 · regional, not allelic
Overall
CADD	27.5	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 P786H vs ClinVar P804H) — 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.Pro804His
Coding: c.2411C>A
MANE Select: NM_001130987
dbSNP: rs768226528
Type: single nucleotide variant
Location: chr2:71564059 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 804: a β-strand

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.Pro804Leu Uncertain significance ★ ⚠ same residue
DYSF p.Pro804Thr 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-pro804his (accessed [today's date]).

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