Is ATOH7 p.Pro9fs (c.26del) pathogenic?

ATOH7 p.Pro9fs (c.26del) is classified Uncertain significance in ATOH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-13). Very rare (popmax 0.000317%, nfe).

How common is ATOH7 p.Pro9fs (c.26del) in the general population?

ATOH7 p.Pro9fs (c.26del) is very rare (popmax 0.000317%, nfe) (gnomAD).

ATOH7 p.Pro9fs

c.26del · rs1419612164 · VCV1449737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000317%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.3	GERP -4.8
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000317% European (non-Finnish) · 3/947,010 alleles

Filtering AF 8.4e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.3e-05%

Overall 0.000256% 3/1,171,626 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.Pro9fs
Coding: c.26del
MANE Select: NM_145178
dbSNP: rs1419612164
Type: Deletion
Location: chr10:68231652 (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.Pro9Leu Uncertain significance ★ ⚠ same residue
ATOH7 p.Pro9= Likely benign ★ same residue
ATOH7 p.Arg41_Arg48del Uncertain significance ★★ same type
ATOH7 p.Gly22_Gly27del Conflicting classifications of pathogenicity ★ same type
ATOH7 p.Lys78_Tyr79del Uncertain significance ★ same type
ATOH7 p.Pro18fs Uncertain significance ★ same type
ATOH7 p.Tyr121fs 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-pro9fs (accessed [today's date]).

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