Is EYS p.Ile2995Val (c.8983A>G) pathogenic?

EYS p.Ile2995Val (c.8983A>G) is classified Uncertain significance in EYS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-21). AlphaMissense: likely benign (0.1096); Absent from gnomAD v4.1.

How common is EYS p.Ile2995Val (c.8983A>G) in the general population?

EYS p.Ile2995Val (c.8983A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EYS p.Ile2995Val (c.8983A>G)?

AlphaMissense predicts likely benign (score 0.1096) — an in-silico prediction, not a clinical call.

EYS p.Ile2995Val

c.8983A>G · rs1009238158 · VCV1903267

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1096 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.1096	likely benign
REVEL	0.296	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -3.2, phastCons 0.99
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	15.64	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 I3016V vs ClinVar I2995V) — 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: EYS
Protein: p.Ile2995Val
Coding: c.8983A>G
MANE Select: NM_001142800
dbSNP: rs1009238158
Type: single nucleotide variant
Location: chr6:63721048 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)

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

Similar variants

EYS p.Ile2995Asn Pathogenic/Likely pathogenic ★★ same residue
EYS p.Ile2995= Uncertain significance ★ same residue
EYS p.Ile2995Thr Uncertain significance ★ same residue
EYS p.Ile2995_Val2996del Pathogenic ★ same residue
EYS p.Ile2995fs Uncertain significance ★ same residue
EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same type
EYS c.1056+3A>C Likely pathogenic ★★ same type
EYS c.1057-1G>A Likely 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/eys-p-ile2995val (accessed [today's date]).

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