Is DYSF p.Ala1024Thr (c.3070G>A) pathogenic?

DYSF p.Ala1024Thr (c.3070G>A) is classified Uncertain significance in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-12). AlphaMissense: likely pathogenic (0.8298); Very rare (popmax 8.47e-05%, nfe); Associated with DYSF-related disorder.

What condition is associated with DYSF p.Ala1024Thr (c.3070G>A)?

DYSF p.Ala1024Thr (c.3070G>A) is associated with DYSF-related disorder (ClinVar).

How common is DYSF p.Ala1024Thr (c.3070G>A) in the general population?

DYSF p.Ala1024Thr (c.3070G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DYSF p.Ala1024Thr (c.3070G>A)?

AlphaMissense predicts likely pathogenic (score 0.8298) — an in-silico prediction, not a clinical call.

DYSF p.Ala1024Thr

c.3070G>A · rs2092344848 · VCV2633299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8298 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DYSF-related disorder

Computational evidence

Protein change
AlphaMissense	0.8298	likely pathogenic
REVEL	0.822	moderately pathogenic-leaning
SaProt	LLR -5.76	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	26.8	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 A1006T vs ClinVar A1024T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,994 alleles

Overall 6.84e-05% 1/1,461,828 alleles · very rare

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.Ala1024Thr
Coding: c.3070G>A
MANE Select: NM_001130987
dbSNP: rs2092344848
Type: single nucleotide variant
Location: chr2:71570319 (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

DYSF-related disorder

Similar variants

DYSF p.Ala1024Pro Uncertain significance ★★ ⚠ same residue
DYSF p.Ala1024= Conflicting classifications of pathogenicity ★ same residue
DYSF c.1380+2T>C Pathogenic ★★ same condition
DYSF p.Gln1341Ter Pathogenic ★★ same condition
DYSF p.Gln1734Ter Pathogenic/Likely pathogenic ★★ same condition
DYSF p.Gln850Ter Pathogenic ★★ same condition
DYSF p.Trp1517Ter Pathogenic ★★ same condition
DYSF p.Thr1122Met 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-ala1024thr (accessed [today's date]).

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