Is ATOSB p.His366Pro (c.1097A>C) pathogenic?

ATOSB p.His366Pro (c.1097A>C) is classified Uncertain significance in ATOSB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: ambiguous (0.4687); Very rare (popmax 0.000254%, nfe).

How common is ATOSB p.His366Pro (c.1097A>C) in the general population?

ATOSB p.His366Pro (c.1097A>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ATOSB p.His366Pro (c.1097A>C)?

AlphaMissense predicts ambiguous (score 0.4687) — an in-silico prediction, not a clinical call.

ATOSB p.His366Pro

c.1097A>C · VCV3453870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4687	ambiguous
REVEL	0.376	indeterminate
SaProt	LLR -8.50	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.76, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 1,348 bp · p 7.4e-07 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,028 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,890 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: ATOSB
Protein: p.His366Pro
Coding: c.1097A>C
MANE Select: NM_025182
Type: single nucleotide variant
Location: chr9:35106373 (GRCh38)
Structure: AlphaFold pLDDT 56.25
Residue 366: the 'required for macropage invasion' region

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

Similar variants

ATOSB p.Ala161Val Uncertain significance ★ ⚠ same type
ATOSB p.Ala194Thr Uncertain significance ★ ⚠ same type
ATOSB p.Ala220Thr Uncertain significance ★ ⚠ same type
ATOSB p.Ala27Ser Uncertain significance ★ ⚠ same type
ATOSB p.Ala6Val Uncertain significance ★ ⚠ same type
ATOSB p.Arg263Gln Uncertain significance ★ ⚠ same type
ATOSB p.Arg263Trp Uncertain significance ★ ⚠ same type
ATOSB p.Arg265His 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/atosb-p-his366pro (accessed [today's date]).

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