Is EYS p.Cys367Ser (c.1100G>C) pathogenic?

EYS p.Cys367Ser (c.1100G>C) is classified Uncertain significance in EYS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-26). AlphaMissense: ambiguous (0.4787); Very rare (popmax 0.00502%, amr); Associated with Inborn genetic diseases.

What condition is associated with EYS p.Cys367Ser (c.1100G>C)?

EYS p.Cys367Ser (c.1100G>C) is associated with Inborn genetic diseases, retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Cys367Ser (c.1100G>C) in the general population?

EYS p.Cys367Ser (c.1100G>C) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about EYS p.Cys367Ser (c.1100G>C)?

AlphaMissense predicts ambiguous (score 0.4787) — an in-silico prediction, not a clinical call.

EYS p.Cys367Ser

c.1100G>C · rs935618633 · VCV839388

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4787	ambiguous
REVEL	0.451	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP -0.43, phastCons 0.015
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	13.16	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 0.00502% Admixed American · 3/59,712 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00067%

Overall 0.00019% 3/1,579,010 alleles · very rare exomes 0/1,427,086 · genomes 3/151,924 · 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.Cys367Ser
Coding: c.1100G>C
MANE Select: NM_001142800
dbSNP: rs935618633
Type: single nucleotide variant
Location: chr6:65402562 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 367: the egf-like 4 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-cys367ser (accessed [today's date]).

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