Is ATOH7 p.Pro145= (c.435C>G) pathogenic?

ATOH7 p.Pro145= (c.435C>G) is classified Likely benign in ATOH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-09). Very rare (popmax 0.00241%, eas).

How common is ATOH7 p.Pro145= (c.435C>G) in the general population?

ATOH7 p.Pro145= (c.435C>G) is very rare (popmax 0.00241%, eas) (gnomAD).

ATOH7 p.Pro145=

c.435C>G · rs748978805 · VCV1647377

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00241%, eas)

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 -6.8	GERP -5
Overall
CADD	2.995	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00241% East Asian · 1/41,510 alleles

Overall 7.09e-05% 1/1,411,332 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.Pro145=
Coding: c.435C>G
MANE Select: NM_145178
dbSNP: rs748978805
Type: single nucleotide variant
Location: chr10:68231243 (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.Pro145Ser 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-pro145 (accessed [today's date]).

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