Is ATOH7 p.Arg34Trp (c.100C>T) pathogenic?

ATOH7 p.Arg34Trp (c.100C>T) is classified Uncertain significance in ATOH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-07). AlphaMissense: likely benign (0.3123); Very rare (popmax 0.000207%, nfe).

How common is ATOH7 p.Arg34Trp (c.100C>T) in the general population?

ATOH7 p.Arg34Trp (c.100C>T) is very rare (popmax 0.000207%, nfe) (gnomAD).

What do computational predictors say about ATOH7 p.Arg34Trp (c.100C>T)?

AlphaMissense predicts likely benign (score 0.3123) — an in-silico prediction, not a clinical call.

ATOH7 p.Arg34Trp

c.100C>T · rs2044027846 · VCV934423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000207%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3123	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -10.30	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -1.2, phastCons 0.98
Regional constraint	o/e 1.06	unconstrained · MANE · 455 bp · p 0.39 · regional, not allelic
Overall
CADD	25.3	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 0.000207% European (non-Finnish) · 2/964,058 alleles

Filtering AF 3.5e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3e-05%

Overall 0.00019% 2/1,053,264 alleles · very rare

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.Arg34Trp
Coding: c.100C>T
MANE Select: NM_145178
dbSNP: rs2044027846
Type: single nucleotide variant
Location: chr10:68231578 (GRCh38)
Gene constraint: LOEUF 1.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.79

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

Similar variants

ATOH7 p.Arg34= Likely benign ★★ same residue
ATOH7 p.Arg34Leu Uncertain significance ★ ⚠ same residue
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.Arg62Ser Uncertain significance ★★ ⚠ same type
ATOH7 p.Arg94Trp 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-arg34trp (accessed [today's date]).

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