Is DYSF p.Pro804Thr (c.2410C>A) pathogenic?

DYSF p.Pro804Thr (c.2410C>A) is classified Uncertain significance in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-29). AlphaMissense: likely benign (0.3152); Very rare (popmax 0.000169%, nfe).

How common is DYSF p.Pro804Thr (c.2410C>A) in the general population?

DYSF p.Pro804Thr (c.2410C>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about DYSF p.Pro804Thr (c.2410C>A)?

AlphaMissense predicts likely benign (score 0.3152) — an in-silico prediction, not a clinical call.

DYSF p.Pro804Thr

c.2410C>A · VCV4072537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3152 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3152	likely benign
REVEL	0.835	moderately pathogenic-leaning
SaProt	LLR -5.76	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 18 kb · p 4.1e-05 · regional, not allelic
Overall
CADD	24.1	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 P786T vs ClinVar P804T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,970 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,066 alleles · very rare exomes 2/1,461,726 · genomes 0/152,340 · 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.Pro804Thr
Coding: c.2410C>A
MANE Select: NM_001130987
Type: single nucleotide variant
Location: chr2:71564058 (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

Similar variants

DYSF p.Pro804His Uncertain significance ★★ ⚠ same residue
DYSF p.Pro804Leu 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-pro804thr (accessed [today's date]).

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