Is EYS p.Ser1010Pro (c.3028T>C) pathogenic?

EYS p.Ser1010Pro (c.3028T>C) is classified Uncertain significance in EYS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-08-21). AlphaMissense: likely benign (0.1992); Ultra-rare (popmax 0.059%, amr); Associated with Inborn genetic diseases.

What condition is associated with EYS p.Ser1010Pro (c.3028T>C)?

EYS p.Ser1010Pro (c.3028T>C) is associated with Inborn genetic diseases (ClinVar).

How common is EYS p.Ser1010Pro (c.3028T>C) in the general population?

EYS p.Ser1010Pro (c.3028T>C) is ultra-rare (popmax 0.059%, amr) (gnomAD).

What do computational predictors say about EYS p.Ser1010Pro (c.3028T>C)?

AlphaMissense predicts likely benign (score 0.1992) — an in-silico prediction, not a clinical call.

EYS p.Ser1010Pro

c.3028T>C · rs557931285 · VCV990481

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1992 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.059%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1992	likely benign
REVEL	0.427	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 3.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	22.6	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 0.059% Admixed American · 30/50,882 alleles

Filtering AF 0.0423% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0368%

Overall 0.00194% 30/1,549,996 alleles · ultra-rare exomes 23/1,397,924 · genomes 7/152,072 · joint denominator

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.Ser1010Pro
Coding: c.3028T>C
MANE Select: NM_001142800
dbSNP: rs557931285
Type: single nucleotide variant
Location: chr6:64822787 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 1010: the egf-like 16; calcium-binding 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.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
EYS p.Ala315Thr 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-ser1010pro (accessed [today's date]).

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