Is EYA4 p.Pro332= (c.996C>T) pathogenic?

EYA4 p.Pro332= (c.996C>T) is classified Likely benign in EYA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-24). No allele count reported in gnomAD v4.1 (AN 1,613,900); Associated with Cardiovascular phenotype.

What condition is associated with EYA4 p.Pro332= (c.996C>T)?

EYA4 p.Pro332= (c.996C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1J (ClinVar).

How common is EYA4 p.Pro332= (c.996C>T) in the general population?

EYA4 p.Pro332= (c.996C>T) is no allele count reported in gnomAD v4.1 (AN 1,613,900) (gnomAD).

EYA4 p.Pro332=

c.996C>T · rs2534855922 · VCV1768760

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,900)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.2	GERP -3.8, phastCons 0.001
Overall
CADD	8.422	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,900). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EYA4
Protein: p.Pro332=
Coding: c.996C>T
MANE Select: NM_004100
dbSNP: rs2534855922
Type: single nucleotide variant
Location: chr6:133481488 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.79
Residue 332: a UniProt-annotated variant site (in dfna10); 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.Pro332Leu Uncertain significance ★ ⚠ same residue
EYA4 p.Pro332Ser 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-pro332 (accessed [today's date]).

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