Is EYA1 p.Pro261= (c.783G>T) pathogenic?

EYA1 p.Pro261= (c.783G>T) is classified Likely benign in EYA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). Very rare (popmax 0.004%, afr); Associated with branchio-oto-renal syndrome.

What condition is associated with EYA1 p.Pro261= (c.783G>T)?

EYA1 p.Pro261= (c.783G>T) is associated with branchio-oto-renal syndrome (ClinVar).

How common is EYA1 p.Pro261= (c.783G>T) in the general population?

EYA1 p.Pro261= (c.783G>T) is very rare (popmax 0.004%, afr) (gnomAD).

EYA1 p.Pro261=

c.783G>T · rs146648560 · VCV1963608

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

branchio-oto-renal syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.5	GERP -3.6
Overall
CADD	0.856	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,002 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,030 alleles · very rare exomes 3/1,461,810 · genomes 0/152,220 · 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: EYA1
Protein: p.Pro261=
Coding: c.783G>T
MANE Select: NM_000503
dbSNP: rs146648560
Type: single nucleotide variant
Location: chr8:71299090 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.68
Residue 261: the 'disordered' region

Full EYA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

branchio-oto-renal syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EYA1 p.Pro261Leu Benign ★★ same residue
EYA1 p.Pro261Thr Uncertain significance ★ ⚠ same residue
EYA1 p.Pro261fs Pathogenic ★ same residue
EYA1 c.1050+1G>T Pathogenic ★★ same condition
EYA1 c.1051-2A>G Pathogenic ★★ same condition
EYA1 c.1199+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYA1 c.1200-1G>A Pathogenic ★★ same condition
EYA1 c.1360+5G>A Pathogenic/Likely pathogenic ★★ 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/eya1-p-pro261 (accessed [today's date]).

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