Is EYS p.Cys768Ser (c.2302T>A) pathogenic?

EYS p.Cys768Ser (c.2302T>A) is classified Uncertain significance in EYS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-27). AlphaMissense: likely pathogenic (0.8148); Ultra-rare (popmax 0.0576%, afr); Associated with Inborn genetic diseases.

What condition is associated with EYS p.Cys768Ser (c.2302T>A)?

EYS p.Cys768Ser (c.2302T>A) is associated with Inborn genetic diseases, retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Cys768Ser (c.2302T>A) in the general population?

EYS p.Cys768Ser (c.2302T>A) is ultra-rare (popmax 0.0576%, afr) (gnomAD).

What do computational predictors say about EYS p.Cys768Ser (c.2302T>A)?

AlphaMissense predicts likely pathogenic (score 0.8148) — an in-silico prediction, not a clinical call.

EYS p.Cys768Ser

c.2302T>A · rs374204063 · VCV938684

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8148 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0576%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8148	likely pathogenic · top 5% in EYS
REVEL	0.513	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -2.5, phastCons 0.001
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	19.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0576% African / African-American · 42/72,896 alleles

Filtering AF 0.0438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0389%

Overall 0.00291% 45/1,549,004 alleles · ultra-rare exomes 18/1,396,952 · genomes 27/152,052 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0576%	1,736
Remaining individualsnot grpmax-eligible	0.00334%	29,979
European (non-Finnish)	8.73e-05%	1,145,206

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.Cys768Ser
Coding: c.2302T>A
MANE Select: NM_001142800
dbSNP: rs374204063
Type: single nucleotide variant
Location: chr6:64945872 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 768: the egf-like 9; calcium-binding domain; a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 25

Similar variants

EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.1056+3A>C Likely pathogenic ★★ same condition
EYS c.1057-1G>A Likely pathogenic ★★ same condition
EYS c.1184+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.1184+1G>T Likely pathogenic ★★ same condition
EYS c.1185-1G>A Likely pathogenic ★★ same condition
EYS c.1299+2T>A Likely pathogenic ★★ same condition
EYS c.1599+1G>T 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-cys768ser (accessed [today's date]).

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