Is EYS p.Trp763Arg (c.2287T>C) pathogenic?

EYS p.Trp763Arg (c.2287T>C) is classified Uncertain significance in EYS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-25). AlphaMissense: likely pathogenic (0.6634); Ultra-rare (popmax 0.0221%, eas); Associated with retinitis pigmentosa.

What condition is associated with EYS p.Trp763Arg (c.2287T>C)?

EYS p.Trp763Arg (c.2287T>C) is associated with retinitis pigmentosa, inherited retinal dystrophy (ClinVar).

How common is EYS p.Trp763Arg (c.2287T>C) in the general population?

EYS p.Trp763Arg (c.2287T>C) is ultra-rare (popmax 0.0221%, eas) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EYS p.Trp763Arg (c.2287T>C)?

AlphaMissense predicts likely pathogenic (score 0.6634) — an in-silico prediction, not a clinical call.

EYS p.Trp763Arg

c.2287T>C · rs886061684 · VCV357729

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6634 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0221%, eas)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.6634	likely pathogenic · top 9% in EYS
REVEL	0.747	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP 1.6, phastCons 0.022
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0221% East Asian · 9/40,768 alleles

Filtering AF 0.0114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00857%

Overall 0.000581% 9/1,548,182 alleles · ultra-rare exomes 9/1,395,990 · genomes 0/152,192 · 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.Trp763Arg
Coding: c.2287T>C
MANE Select: NM_001142800
dbSNP: rs886061684
Type: single nucleotide variant
Location: chr6:64945887 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 763: the egf-like 9; calcium-binding domain

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited retinal dystrophy

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

EYS p.Trp763Gly Uncertain significance ★★ same residue
EYS p.Trp763Ter Pathogenic ★ same residue
EYS p.Trp763Cys Uncertain significance ★ ⚠ same residue
EYS p.Trp763Leu Uncertain significance ★ same residue
EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.1299+1G>T Pathogenic/Likely pathogenic ★★ same condition
EYS c.1766+1G>T Pathogenic/Likely pathogenic ★★ same condition
EYS c.2259+1G>A 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-trp763arg (accessed [today's date]).

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