Is EYA4 p.Ser243= (c.729T>C) pathogenic?

EYA4 p.Ser243= (c.729T>C) is classified Likely benign in EYA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). Very rare (popmax 0.000125%); Associated with dilated cardiomyopathy 1J.

What condition is associated with EYA4 p.Ser243= (c.729T>C)?

EYA4 p.Ser243= (c.729T>C) is associated with dilated cardiomyopathy 1J (ClinVar).

How common is EYA4 p.Ser243= (c.729T>C) in the general population?

EYA4 p.Ser243= (c.729T>C) is very rare (popmax 0.000125%) (gnomAD).

EYA4 p.Ser243=

Q: How is Sensorineural deafness with dilated cardiomyopathy inherited?

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

c.729T>C · rs1794703368 · VCV1145998

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000125%)

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 1.1	GERP -0.87, phastCons 1
Overall
CADD	10.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000125%

Overall 0.000125% 2/1,599,102 alleles · very rare exomes 2/1,446,770 · genomes 0/152,332 · 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.Ser243=
Coding: c.729T>C
MANE Select: NM_004100
dbSNP: rs1794703368
Type: single nucleotide variant
Location: chr6:133464783 (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 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-ser243 (accessed [today's date]).

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