Is ATOH1 p.Ala282= (c.846G>C) pathogenic?

ATOH1 p.Ala282= (c.846G>C) is classified Likely benign in ATOH1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-02). Ultra-rare (popmax 0.0613%, amr); Associated with ATOH1-related disorder.

What condition is associated with ATOH1 p.Ala282= (c.846G>C)?

ATOH1 p.Ala282= (c.846G>C) is associated with ATOH1-related disorder (ClinVar).

How common is ATOH1 p.Ala282= (c.846G>C) in the general population?

ATOH1 p.Ala282= (c.846G>C) is ultra-rare (popmax 0.0613%, amr) (gnomAD).

ATOH1 p.Ala282=

c.846G>C · rs752679675 · VCV3039537

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0613%, amr)

Conditions

ATOH1-related disorder

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 -2.1	GERP -4.4
Overall
CADD	2.893	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0613% Admixed American · 36/58,772 alleles

Filtering AF 0.0455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.04%

Overall 0.0103% 166/1,604,754 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0613%	1,633
Middle Eastern	0.0499%	2,003
Remaining individualsnot grpmax-eligible	0.0483%	2,068
European (non-Finnish)	0.00817%	12,246
African / African-American	0.00134%	74,778

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: ATOH1
Protein: p.Ala282=
Coding: c.846G>C
MANE Select: NM_005172
dbSNP: rs752679675
Type: single nucleotide variant
Location: chr4:93829772 (GRCh38)
Gene constraint: LOEUF 0.767 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 60.06

Full ATOH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ATOH1-related disorder

Similar variants

ATOH1 p.Pro148Ser Uncertain significance ⚠ same condition
ATOH1 p.Pro25Ala Uncertain significance ⚠ same condition
ATOH1 p.Glu45= Likely benign same condition
ATOH1 p.Pro225Arg Likely benign ⚠ same condition
ATOH1 p.Pro50= Benign same condition
ATOH1 p.His344fs Pathogenic ★ same condition
ATOH1 p.Ala253fs Uncertain significance ★ same condition
ATOH1 p.Arg161Gly Uncertain significance ★★ ⚠ same type

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/atoh1-p-ala282 (accessed [today's date]).

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