Is ATOH7 p.Pro68Ala (c.202C>G) pathogenic?

ATOH7 p.Pro68Ala (c.202C>G) is classified Uncertain significance in ATOH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-12). AlphaMissense: likely pathogenic (0.9968); Absent from gnomAD v4.1.

How common is ATOH7 p.Pro68Ala (c.202C>G) in the general population?

ATOH7 p.Pro68Ala (c.202C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATOH7 p.Pro68Ala (c.202C>G)?

AlphaMissense predicts likely pathogenic (score 0.9968) — an in-silico prediction, not a clinical call.

ATOH7 p.Pro68Ala

c.202C>G · rs1196140587 · VCV2080669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9968 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9968	likely pathogenic · top 6% in ATOH7
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -16.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 455 bp · p 0.39 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATOH7
Protein: p.Pro68Ala
Coding: c.202C>G
MANE Select: NM_145178
dbSNP: rs1196140587
Type: single nucleotide variant
Location: chr10:68231476 (GRCh38)
Gene constraint: LOEUF 1.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.79
Residue 68: the bhlh domain

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

Similar variants

ATOH7 p.Pro68= Benign/Likely benign ★★ same residue
ATOH7 p.Pro68Arg Uncertain significance ★ ⚠ same residue
ATOH7 p.Pro68Ser 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

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-pro68ala (accessed [today's date]).

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