Is EYA1 p.Pro85= (c.255A>G) pathogenic?

EYA1 p.Pro85= (c.255A>G) is classified Likely benign in EYA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). Very rare (popmax 0.000848%, nfe); Associated with branchio-oto-renal syndrome.

What condition is associated with EYA1 p.Pro85= (c.255A>G)?

EYA1 p.Pro85= (c.255A>G) is associated with branchio-oto-renal syndrome (ClinVar).

How common is EYA1 p.Pro85= (c.255A>G) in the general population?

EYA1 p.Pro85= (c.255A>G) is very rare (popmax 0.000848%, nfe) (gnomAD).

EYA1 p.Pro85=

c.255A>G · rs61753262 · VCV2193546

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

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 2.4	GERP 0.54, phastCons 1
Overall
CADD	8.731	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,682 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00062% 10/1,613,786 alleles · very rare exomes 10/1,461,456 · 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: EYA1
Protein: p.Pro85=
Coding: c.255A>G
MANE Select: NM_000503
dbSNP: rs61753262
Type: single nucleotide variant
Location: chr8:71322216 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.68
Residue 85: 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 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
EYA1 c.1361-1G>A Pathogenic ★★ same condition
EYA1 c.1597+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYA1 c.1698+1G>T 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-pro85 (accessed [today's date]).

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