Is EYA4 p.Pro362= (c.1086G>A) pathogenic?

EYA4 p.Pro362= (c.1086G>A) is classified Likely benign in EYA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-07). Very rare (popmax 0.00329%, sas); Associated with Cardiovascular phenotype.

What condition is associated with EYA4 p.Pro362= (c.1086G>A)?

EYA4 p.Pro362= (c.1086G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1J (ClinVar).

How common is EYA4 p.Pro362= (c.1086G>A) in the general population?

EYA4 p.Pro362= (c.1086G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

EYA4 p.Pro362=

c.1086G>A · rs763081961 · VCV2079875

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

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 -8.6	GERP -5.7
Overall
CADD	2.243	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,078 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000744% 12/1,613,738 alleles · very rare exomes 11/1,461,730 · genomes 1/152,008 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,359
African / African-American	0.00267%	37,425
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000509%	196,649

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: EYA4
Protein: p.Pro362=
Coding: c.1086G>A
MANE Select: NM_004100
dbSNP: rs763081961
Type: single nucleotide variant
Location: chr6:133481578 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.79
Residue 362: 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.Pro362Leu Uncertain significance ★★ ⚠ same residue
EYA4 p.Pro362fs Pathogenic ★ 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-pro362 (accessed [today's date]).

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