Is EYA4 p.Pro102Ser (c.304C>T) pathogenic?

EYA4 p.Pro102Ser (c.304C>T) is classified Uncertain significance in EYA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-02). AlphaMissense: likely benign (0.1931); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with EYA4 p.Pro102Ser (c.304C>T)?

EYA4 p.Pro102Ser (c.304C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is EYA4 p.Pro102Ser (c.304C>T) in the general population?

EYA4 p.Pro102Ser (c.304C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EYA4 p.Pro102Ser (c.304C>T)?

AlphaMissense predicts likely benign (score 0.1931) — an in-silico prediction, not a clinical call.

EYA4 p.Pro102Ser

c.304C>T · rs756612363 · VCV1799241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1931 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1931	likely benign
REVEL	0.489	indeterminate
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 254 kb · p 0.0025 · regional, not allelic
Overall
CADD	26.0	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: EYA4
Protein: p.Pro102Ser
Coding: c.304C>T
MANE Select: NM_004100
dbSNP: rs756612363
Type: single nucleotide variant
Location: chr6:133456582 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.79

Full EYA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EYA4 p.Pro102= Likely benign ★ same residue
EYA4 p.Pro102Leu Uncertain significance ★ ⚠ same residue
EYA4 p.Pro102Thr Uncertain significance ★ ⚠ same residue
EYA4 c.1739-1G>A Likely pathogenic ★★ same condition
EYA4 c.-2A>G Uncertain significance ★★ same condition
EYA4 p.Ala253Thr Uncertain significance ★★ ⚠ same condition
EYA4 p.Ala287Val Uncertain significance ★★ ⚠ same condition
EYA4 p.Ala292Thr 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/eya4-p-pro102ser (accessed [today's date]).

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