Is EYA2 p.Pro88Ser (c.262C>T) pathogenic?

EYA2 p.Pro88Ser (c.262C>T) is classified Uncertain significance in EYA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-05). AlphaMissense: likely benign (0.0686); Ultra-rare (popmax 0.0187%, sas).

How common is EYA2 p.Pro88Ser (c.262C>T) in the general population?

EYA2 p.Pro88Ser (c.262C>T) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

What do computational predictors say about EYA2 p.Pro88Ser (c.262C>T)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

EYA2 p.Pro88Ser

c.262C>T · rs556437135 · VCV2520274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.543	indeterminate
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 99 kb · p 0.41 · regional, not allelic
Overall
CADD	24.5	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/91,078 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00976%

Overall 0.00105% 17/1,613,794 alleles · ultra-rare exomes 16/1,461,606 · genomes 1/152,188 · 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: EYA2
Protein: p.Pro88Ser
Coding: c.262C>T
MANE Select: NM_005244
dbSNP: rs556437135
Type: single nucleotide variant
Location: chr20:47005048 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.07 · 7 PDB

Full EYA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EYA2 p.Gly251Cys Uncertain significance ★★ ⚠ same type
EYA2 p.Ala93Thr Benign ★★ same type
EYA2 p.Thr238Ala Benign ★★ same type
EYA2 p.Ala153Thr Uncertain significance ★ ⚠ same type
EYA2 p.Ala359Val Uncertain significance ★ ⚠ same type
EYA2 p.Ala524Thr Uncertain significance ★ ⚠ same type
EYA2 p.Ala76Gly Uncertain significance ★ ⚠ same type
EYA2 p.Arg243Gln Uncertain significance ★ ⚠ same type

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/eya2-p-pro88ser (accessed [today's date]).

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