Is ATOH7 p.Ser3Phe (c.8C>T) pathogenic?

ATOH7 p.Ser3Phe (c.8C>T) is classified Uncertain significance in ATOH7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-05). AlphaMissense: likely benign (0.2001); Rare (popmax 0.138%, mid).

How common is ATOH7 p.Ser3Phe (c.8C>T) in the general population?

ATOH7 p.Ser3Phe (c.8C>T) is rare (popmax 0.138%, mid) (gnomAD).

What do computational predictors say about ATOH7 p.Ser3Phe (c.8C>T)?

AlphaMissense predicts likely benign (score 0.2001) — an in-silico prediction, not a clinical call.

ATOH7 p.Ser3Phe

c.8C>T · rs1032692523 · VCV1052724

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2001 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2001	likely benign
REVEL	0.329	indeterminate
SaProt	LLR -8.20	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 9.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 455 bp · p 0.39 · regional, not allelic
Overall
CADD	27.5	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

Grpmax group 0.138% Middle Eastern · 4/2,890 alleles

Filtering AF 0.0473% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.00475% 56/1,179,862 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.138%	723
Ashkenazi Jewishnot grpmax-eligible	0.0328%	3,052
Remaining individualsnot grpmax-eligible	0.0169%	5,921
African / African-American	0.00642%	15,572
European (non-Finnish)	0.00379%	26,376

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.Ser3Phe
Coding: c.8C>T
MANE Select: NM_145178
dbSNP: rs1032692523
Type: single nucleotide variant
Location: chr10:68231670 (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.Ser3Pro 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
ATOH7 p.Asn46Ser 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-ser3phe (accessed [today's date]).

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