Is EYS p.Asp2969Val (c.8906A>T) pathogenic?

EYS p.Asp2969Val (c.8906A>T) is classified Uncertain significance in EYS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely pathogenic (0.784); Very rare (popmax 0.000174%, nfe); Associated with EYS-related disorder.

What condition is associated with EYS p.Asp2969Val (c.8906A>T)?

EYS p.Asp2969Val (c.8906A>T) is associated with EYS-related disorder (ClinVar).

How common is EYS p.Asp2969Val (c.8906A>T) in the general population?

EYS p.Asp2969Val (c.8906A>T) is very rare (popmax 0.000174%, nfe) (gnomAD).

What do computational predictors say about EYS p.Asp2969Val (c.8906A>T)?

AlphaMissense predicts likely pathogenic (score 0.784) — an in-silico prediction, not a clinical call.

EYS p.Asp2969Val

c.8906A>T · rs1768366640 · VCV2636212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.784 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Conditions

EYS-related disorder

Computational evidence

Protein change
AlphaMissense	0.784	likely pathogenic · top 6% in EYS
REVEL	0.461	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.39, phastCons 0.58
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D2990V vs ClinVar D2969V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,146,752 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000129% 2/1,551,442 alleles · very rare exomes 2/1,399,168 · genomes 0/152,274 · 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: EYS
Protein: p.Asp2969Val
Coding: c.8906A>T
MANE Select: NM_001142800
dbSNP: rs1768366640
Type: single nucleotide variant
Location: chr6:63721125 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)

Full EYS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EYS-related disorder

Similar variants

EYS p.Asp2969= Likely benign ★ same residue
EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.1766+1G>T Pathogenic/Likely pathogenic ★★ same condition
EYS c.2381+1G>A Likely pathogenic ★★ same condition
EYS c.2641+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.2738+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3443+1G>A Pathogenic ★★ same condition
EYS c.3443+1G>T Pathogenic/Likely pathogenic ★★ 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/eys-p-asp2969val (accessed [today's date]).

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