Is EYA4 p.Ser462= (c.1386T>C) pathogenic?

EYA4 p.Ser462= (c.1386T>C) is classified Likely benign in EYA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-24). Very rare (popmax 8.47e-05%, nfe); Associated with dilated cardiomyopathy 1J.

What condition is associated with EYA4 p.Ser462= (c.1386T>C)?

EYA4 p.Ser462= (c.1386T>C) is associated with dilated cardiomyopathy 1J (ClinVar).

How common is EYA4 p.Ser462= (c.1386T>C) in the general population?

EYA4 p.Ser462= (c.1386T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

EYA4 p.Ser462=

Q: How is Sensorineural deafness with dilated cardiomyopathy inherited?

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

c.1386T>C · rs2535339655 · VCV2737571

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

dilated cardiomyopathy 1J

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.1	GERP 2.1, phastCons 1
Overall
CADD	12.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,008 alleles

Overall 6.2e-05% 1/1,614,164 alleles · very rare exomes 1/1,461,834 · genomes 0/152,330 · 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.Ser462=
Coding: c.1386T>C
MANE Select: NM_004100
dbSNP: rs2535339655
Type: single nucleotide variant
Location: chr6:133512923 (GRCh38)

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

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-ser462 (accessed [today's date]).

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