Is EYS p.Ser1867Phe (c.5600C>T) pathogenic?

EYS p.Ser1867Phe (c.5600C>T) is classified Conflicting classifications of pathogenicity in EYS (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.1407); Rare (popmax 0.281%, sas); Associated with retinitis pigmentosa.

What condition is associated with EYS p.Ser1867Phe (c.5600C>T)?

EYS p.Ser1867Phe (c.5600C>T) is associated with retinitis pigmentosa (ClinVar).

How common is EYS p.Ser1867Phe (c.5600C>T) in the general population?

EYS p.Ser1867Phe (c.5600C>T) is rare (popmax 0.281%, sas) (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.Ser1867Phe (c.5600C>T)?

AlphaMissense predicts likely benign (score 0.1407) — an in-silico prediction, not a clinical call.

EYS p.Ser1867Phe

c.5600C>T · rs542339299 · VCV760696

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1407 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.281%, sas)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.1407	likely benign
REVEL	0.395	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	phastCons 0.96
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	22.4	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 0.281% South Asian · 236/83,968 alleles

Filtering AF 0.252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.24%

Overall 0.0157% 244/1,550,710 alleles · rare exomes 233/1,398,460 · genomes 11/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.281%	356
Remaining individualsnot grpmax-eligible	0.0117%	8,580
European (non-Finnish)	8.72e-05%	1,146,414

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.Ser1867Phe
Coding: c.5600C>T
MANE Select: NM_001142800
dbSNP: rs542339299
Type: single nucleotide variant
Location: chr6:64590267 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)

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

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.Ser1867Tyr Uncertain significance ★★ same residue
EYS p.Ser1867= Likely benign ★★ same residue
EYS c.1056+1G>A 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
EYS c.3164+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3243+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3443+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-ser1867phe (accessed [today's date]).

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