Is EYA1 p.Ser49= (c.147C>T) pathogenic?

EYA1 p.Ser49= (c.147C>T) is classified Benign/Likely benign in EYA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-09). Ultra-rare (popmax 0.0803%, eas); Associated with branchio-oto-renal syndrome.

What condition is associated with EYA1 p.Ser49= (c.147C>T)?

EYA1 p.Ser49= (c.147C>T) is associated with branchio-oto-renal syndrome (ClinVar).

How common is EYA1 p.Ser49= (c.147C>T) in the general population?

EYA1 p.Ser49= (c.147C>T) is ultra-rare (popmax 0.0803%, eas) (gnomAD).

EYA1 p.Ser49=

c.147C>T · rs771141271 · VCV2197800

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0803%, eas)

Conditions

branchio-oto-renal syndrome

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 9.9	GERP 2, phastCons 1
Overall
CADD	13.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0803% East Asian · 36/44,844 alleles

Filtering AF 0.0596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00242% 39/1,613,146 alleles · ultra-rare exomes 32/1,460,998 · genomes 7/152,148 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0803%	1,246
Remaining individualsnot grpmax-eligible	0.0048%	20,819

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.Ser49=
Coding: c.147C>T
MANE Select: NM_000503
dbSNP: rs771141271
Type: single nucleotide variant
Location: chr8:71334152 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.68
Residue 49: 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-ser49 (accessed [today's date]).

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