Is ATOH7 p.Arg62Ser (c.184C>A) pathogenic?

ATOH7 p.Arg62Ser (c.184C>A) is classified Uncertain significance in ATOH7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-12). AlphaMissense: likely pathogenic (0.6516); Ultra-rare (popmax 0.0271%, nfe).

How common is ATOH7 p.Arg62Ser (c.184C>A) in the general population?

ATOH7 p.Arg62Ser (c.184C>A) is ultra-rare (popmax 0.0271%, nfe) (gnomAD).

What do computational predictors say about ATOH7 p.Arg62Ser (c.184C>A)?

AlphaMissense predicts likely pathogenic (score 0.6516) — an in-silico prediction, not a clinical call.

ATOH7 p.Arg62Ser

c.184C>A · rs373272132 · VCV848320

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6516 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0271%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6516	likely pathogenic
REVEL	0.421	indeterminate
SaProt	LLR -8.78	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.36	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 6.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 455 bp · p 0.39 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0271% European (non-Finnish) · 314/1,160,612 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0236%

Overall 0.0215% 339/1,575,334 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0271%	3,696
Admixed American	0.0199%	5,034
Remaining individualsnot grpmax-eligible	0.0149%	6,729
African / African-American	0.00694%	14,410

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: ATOH7
Protein: p.Arg62Ser
Coding: c.184C>A
MANE Select: NM_145178
dbSNP: rs373272132
Type: single nucleotide variant
Location: chr10:68231494 (GRCh38)
Gene constraint: LOEUF 1.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.79
Residue 62: the bhlh domain

Full ATOH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATOH7 p.Ala20Gly Uncertain significance ★★ ⚠ same type
ATOH7 p.Ala20Thr Uncertain significance ★★ ⚠ same type
ATOH7 p.Ala44Glu Uncertain significance ★★ ⚠ same type
ATOH7 p.Ala59Val Uncertain significance ★★ ⚠ same type
ATOH7 p.Arg94Trp Uncertain significance ★★ ⚠ same type
ATOH7 p.Asn46Ser Uncertain significance ★★ ⚠ same type
ATOH7 p.Asn57Ser Uncertain significance ★★ ⚠ same type
ATOH7 p.Asp119Gly 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/atoh7-p-arg62ser (accessed [today's date]).

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