Is EYA4 p.Ser256= (c.768A>C) pathogenic?

EYA4 p.Ser256= (c.768A>C) is classified Likely benign in EYA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-06). No allele count reported in gnomAD v4.1 (AN 1,611,622); Associated with Cardiovascular phenotype.

What condition is associated with EYA4 p.Ser256= (c.768A>C)?

EYA4 p.Ser256= (c.768A>C) is associated with Cardiovascular phenotype (ClinVar).

How common is EYA4 p.Ser256= (c.768A>C) in the general population?

EYA4 p.Ser256= (c.768A>C) is no allele count reported in gnomAD v4.1 (AN 1,611,622) (gnomAD).

EYA4 p.Ser256=

c.768A>C · rs147135637 · VCV1760133

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,622)

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 -0.14	GERP -2.1, phastCons 0.008
Overall
CADD	7.729	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,622). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EYA4
Protein: p.Ser256=
Coding: c.768A>C
MANE Select: NM_004100
dbSNP: rs147135637
Type: single nucleotide variant
Location: chr6:133464822 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EYA4 c.1739-1G>A Likely pathogenic ★★ same condition
EYA4 c.-2A>G Uncertain significance ★★ same condition
EYA4 p.Ala253Thr Uncertain significance ★★ ⚠ same condition
EYA4 p.Ala287Val Uncertain significance ★★ ⚠ same condition
EYA4 p.Ala292Thr Uncertain significance ★★ ⚠ same condition
EYA4 p.Ala402Ser Uncertain significance ★★ ⚠ same condition
EYA4 p.Ala516Thr Uncertain significance ★★ ⚠ same condition
EYA4 p.Ala79Thr 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-ser256 (accessed [today's date]).

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