Is EYS p.Ser2744Pro (c.8230T>C) pathogenic?

EYS p.Ser2744Pro (c.8230T>C) is classified Uncertain significance in EYS (ClinVar, Single submitter, 2 submitters; last evaluated 2020-11-18). AlphaMissense: likely benign (0.303); Absent from gnomAD v4.1; Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Ser2744Pro (c.8230T>C)?

EYS p.Ser2744Pro (c.8230T>C) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Ser2744Pro (c.8230T>C) in the general population?

EYS p.Ser2744Pro (c.8230T>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.Ser2744Pro (c.8230T>C)?

AlphaMissense predicts likely benign (score 0.303) — an in-silico prediction, not a clinical call.

EYS p.Ser2744Pro

c.8230T>C · rs1768622052 · VCV1038035

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.303 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

retinitis pigmentosa 25

Computational evidence

Protein change
AlphaMissense	0.303	likely benign
REVEL	0.552	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.1, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S2765P vs ClinVar S2744P) — verify the residue.

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.Ser2744Pro
Coding: c.8230T>C
MANE Select: NM_001142800
dbSNP: rs1768622052
Type: single nucleotide variant
Location: chr6:63726522 (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 25 — 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.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-ser2744pro (accessed [today's date]).

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