Is EYS p.Ser2455Pro (c.7363T>C) pathogenic?

EYS p.Ser2455Pro (c.7363T>C) is classified Uncertain significance in EYS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: ambiguous (0.4109); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EYS p.Ser2455Pro (c.7363T>C)?

EYS p.Ser2455Pro (c.7363T>C) is associated with Inborn genetic diseases (ClinVar).

How common is EYS p.Ser2455Pro (c.7363T>C) in the general population?

EYS p.Ser2455Pro (c.7363T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EYS p.Ser2455Pro (c.7363T>C)?

AlphaMissense predicts ambiguous (score 0.4109) — an in-silico prediction, not a clinical call.

EYS p.Ser2455Pro

c.7363T>C · VCV4252221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4109 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4109	ambiguous
REVEL	0.312	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	24.1	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

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.Ser2455Pro
Coding: c.7363T>C
MANE Select: NM_001142800
Type: single nucleotide variant
Location: chr6:63806238 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 2455: the laminin g-like 3 domain

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

Similar variants

EYS p.Ser2455= Likely benign ★ same residue
EYS p.Ala1174Glu Uncertain significance ★★ same condition
EYS p.Ala1465Thr Uncertain significance ★★ ⚠ same condition
EYS p.Ala1520Asp Uncertain significance ★★ ⚠ same condition
EYS p.Ala1520Gly Uncertain significance ★★ ⚠ same condition
EYS p.Ala1984Thr Uncertain significance ★★ same condition
EYS p.Ala2728Val Uncertain significance ★★ ⚠ same condition
EYS p.Ala2729Val Uncertain significance ★★ ⚠ 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-ser2455pro (accessed [today's date]).

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