Is ATOH7 p.Pro145Ser (c.433C>T) pathogenic?

ATOH7 p.Pro145Ser (c.433C>T) is classified Uncertain significance in ATOH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely benign (0.1035); Absent from gnomAD v4.1.

How common is ATOH7 p.Pro145Ser (c.433C>T) in the general population?

ATOH7 p.Pro145Ser (c.433C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATOH7 p.Pro145Ser (c.433C>T)?

AlphaMissense predicts likely benign (score 0.1035) — an in-silico prediction, not a clinical call.

ATOH7 p.Pro145Ser

c.433C>T · VCV4171299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1035 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,567,726)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1035	likely benign
REVEL	0.38	indeterminate
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 2.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 455 bp · p 0.39 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,567,726). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATOH7
Protein: p.Pro145Ser
Coding: c.433C>T
MANE Select: NM_145178
Type: single nucleotide variant
Location: chr10:68231245 (GRCh38)
Gene constraint: LOEUF 1.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.79
Residue 145: a UniProt-annotated variant site (in phpvar; uncertain significance)

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

Similar variants

ATOH7 p.Pro145Ala Uncertain significance ★★ ⚠ same residue
ATOH7 p.Pro145Arg Uncertain significance ★ ⚠ same residue
ATOH7 p.Pro145= Likely benign ★ 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-pro145ser (accessed [today's date]).

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