Is EYS p.Arg2540Ser (c.7620A>C) pathogenic?

EYS p.Arg2540Ser (c.7620A>C) is classified Uncertain significance in EYS (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.165); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with EYS p.Arg2540Ser (c.7620A>C)?

EYS p.Arg2540Ser (c.7620A>C) is associated with retinitis pigmentosa (ClinVar).

How common is EYS p.Arg2540Ser (c.7620A>C) in the general population?

EYS p.Arg2540Ser (c.7620A>C) is absent from gnomAD v4.1 (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.Arg2540Ser (c.7620A>C)?

AlphaMissense predicts likely benign (score 0.165) — an in-silico prediction, not a clinical call.

EYS p.Arg2540Ser

c.7620A>C · rs886061667 · VCV357690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.165 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.165	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	GERP -1.2, phastCons 0.88
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	13.44	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EYS
Protein: p.Arg2540Ser
Coding: c.7620A>C
MANE Select: NM_001142800
dbSNP: rs886061667
Type: single nucleotide variant
Location: chr6:63788208 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 2540: the laminin g-like 3 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

For Retinitis pigmentosa (Orphanet):

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

Similar variants

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
EYS c.5928-2A>G Pathogenic ★★ same condition
EYS c.6191+2T>C 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-arg2540ser (accessed [today's date]).

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