Is EYA3 p.Ser264Phe (c.791C>T) pathogenic?

EYA3 p.Ser264Phe (c.791C>T) is classified Uncertain significance in EYA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely benign (0.0907); Absent from gnomAD v4.1.

How common is EYA3 p.Ser264Phe (c.791C>T) in the general population?

EYA3 p.Ser264Phe (c.791C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EYA3 p.Ser264Phe (c.791C>T)?

AlphaMissense predicts likely benign (score 0.0907) — an in-silico prediction, not a clinical call.

EYA3 p.Ser264Phe

c.791C>T · VCV3846923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0907 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0907	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -9.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 47 kb · p 0.034 · regional, not allelic
Overall
CADD	24.7	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

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: EYA3
Protein: p.Ser264Phe
Coding: c.791C>T
MANE Select: NM_001990
Type: single nucleotide variant
Location: chr1:28011065 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 66.28 · 2 PDB
Residue 264: the 'disordered' region

Full EYA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EYA3 c.1083+2T>C Uncertain significance ★ same type
EYA3 p.Ala187Val Uncertain significance ★ ⚠ same type
EYA3 p.Ala463Val Uncertain significance ★ ⚠ same type
EYA3 p.Arg253Ser Uncertain significance ★ ⚠ same type
EYA3 p.Arg279Lys Uncertain significance ★ ⚠ same type
EYA3 p.Arg287Gln Uncertain significance ★ same type
EYA3 p.Arg287Trp Uncertain significance ★ ⚠ same type
EYA3 p.Arg420Gln 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/eya3-p-ser264phe (accessed [today's date]).

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