Is EYA4 p.Ala79= (c.237A>G) pathogenic?

EYA4 p.Ala79= (c.237A>G) is classified Likely benign in EYA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-28). Very rare (popmax 0.00333%, amr); Associated with dilated cardiomyopathy 1J.

What condition is associated with EYA4 p.Ala79= (c.237A>G)?

EYA4 p.Ala79= (c.237A>G) is associated with dilated cardiomyopathy 1J (ClinVar).

How common is EYA4 p.Ala79= (c.237A>G) in the general population?

EYA4 p.Ala79= (c.237A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

EYA4 p.Ala79=

Q: How is Sensorineural deafness with dilated cardiomyopathy inherited?

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

c.237A>G · rs727504840 · VCV179394

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

dilated cardiomyopathy 1J

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 0.55, phastCons 1
Overall
CADD	17.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,022 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,894 alleles · very rare exomes 2/1,461,582 · genomes 0/152,312 · 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.Ala79=
Coding: c.237A>G
MANE Select: NM_004100
dbSNP: rs727504840
Type: single nucleotide variant
Location: chr6:133448139 (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

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 p.Ala79Thr Uncertain significance ★★ ⚠ same residue
EYA4 p.Ala79Val 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-ala79 (accessed [today's date]).

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