Is EYS p.Ser2650Phe (c.7949C>T) pathogenic?

EYS p.Ser2650Phe (c.7949C>T) is classified Conflicting classifications of pathogenicity in EYS (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-09-24). AlphaMissense: likely benign (0.299); Ultra-rare (popmax 0.0269%, eas); Associated with inherited retinal dystrophy.

What condition is associated with EYS p.Ser2650Phe (c.7949C>T)?

EYS p.Ser2650Phe (c.7949C>T) is associated with inherited retinal dystrophy, retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Ser2650Phe (c.7949C>T) in the general population?

EYS p.Ser2650Phe (c.7949C>T) is ultra-rare (popmax 0.0269%, eas) (gnomAD).

What do computational predictors say about EYS p.Ser2650Phe (c.7949C>T)?

AlphaMissense predicts likely benign (score 0.299) — an in-silico prediction, not a clinical call.

EYS p.Ser2650Phe

c.7949C>T · rs374714909 · VCV636169

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.299 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0269%, eas)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.299	likely benign
REVEL	0.534	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.1, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	24.9	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 0.0269% East Asian · 11/40,896 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0011% 17/1,550,336 alleles · ultra-rare exomes 12/1,398,290 · genomes 5/152,046 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0269%	3,718
Remaining individualsnot grpmax-eligible	0.00833%	12,005
European (non-Finnish)	8.72e-05%	1,146,142

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.Ser2650Phe
Coding: c.7949C>T
MANE Select: NM_001142800
dbSNP: rs374714909
Type: single nucleotide variant
Location: chr6:63762583 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 2650: the egf-like 25 domain

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 25

Similar variants

EYS p.Ser2650= Likely benign ★ same residue
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+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-ser2650phe (accessed [today's date]).

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