Is EYA4 p.Pro229= (c.687A>G) pathogenic?

EYA4 p.Pro229= (c.687A>G) is classified Likely benign in EYA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-23). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with EYA4 p.Pro229= (c.687A>G)?

EYA4 p.Pro229= (c.687A>G) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1J (ClinVar).

How common is EYA4 p.Pro229= (c.687A>G) in the general population?

EYA4 p.Pro229= (c.687A>G) is absent from gnomAD v4.1 (gnomAD).

EYA4 p.Pro229=

c.687A>G · rs2534568737 · VCV2861090

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -5.7
Overall
CADD	3.781	PHRED · no single calibrated threshold — expert panels disagree

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.Pro229=
Coding: c.687A>G
MANE Select: NM_004100
dbSNP: rs2534568737
Type: single nucleotide variant
Location: chr6:133462727 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.79
Residue 229: the 'disordered' region

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

Also linked: dilated cardiomyopathy 1J

Similar variants

EYA4 p.Pro229Gln Uncertain significance ★★ ⚠ same residue
EYA4 p.Pro229Leu Uncertain significance ★★ ⚠ same residue
EYA4 c.1341-2A>G Likely pathogenic ★★ same condition
EYA4 c.1739-1G>A Likely pathogenic ★★ same condition
EYA4 p.Asp194Asn Pathogenic/Likely pathogenic ★★ ⚠ same condition
EYA4 p.Trp81Ter Pathogenic/Likely pathogenic ★★ same condition
EYA4 c.1282-13A>G Uncertain significance ★★ same condition
EYA4 c.1340+3A>G 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-pro229 (accessed [today's date]).

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