Is EYA4 p.Pro569= (c.1707C>T) pathogenic?

EYA4 p.Pro569= (c.1707C>T) is classified Likely benign in EYA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-06). Very rare (popmax 0.00267%, afr); Associated with dilated cardiomyopathy 1J.

What condition is associated with EYA4 p.Pro569= (c.1707C>T)?

EYA4 p.Pro569= (c.1707C>T) is associated with dilated cardiomyopathy 1J (ClinVar).

How common is EYA4 p.Pro569= (c.1707C>T) in the general population?

EYA4 p.Pro569= (c.1707C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

EYA4 p.Pro569=

Q: How is Sensorineural deafness with dilated cardiomyopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1707C>T · rs1197553602 · VCV1095933

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

dilated cardiomyopathy 1J

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 2.7	GERP 1.2, phastCons 1
Overall
CADD	13.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,840 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,612,152 alleles · very rare exomes 1/1,460,018 · genomes 1/152,134 · joint denominator

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.Pro569=
Coding: c.1707C>T
MANE Select: NM_004100
dbSNP: rs1197553602
Type: single nucleotide variant
Location: chr6:133523146 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.79
Residue 569: a UniProt-annotated variant site (in dfna10)

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

Disease context

dilated cardiomyopathy 1J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sensorineural deafness with dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

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
EYA4 c.970+5A>G Uncertain significance ★★ same condition
EYA4 c.971-3T>C 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-pro569 (accessed [today's date]).

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