Is ATOSB p.Arg490Gln (c.1469G>A) pathogenic?

ATOSB p.Arg490Gln (c.1469G>A) is classified Uncertain significance in ATOSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.0925); Very rare (popmax 0.00756%, nfe).

How common is ATOSB p.Arg490Gln (c.1469G>A) in the general population?

ATOSB p.Arg490Gln (c.1469G>A) is very rare (popmax 0.00756%, nfe) (gnomAD).

What do computational predictors say about ATOSB p.Arg490Gln (c.1469G>A)?

AlphaMissense predicts likely benign (score 0.0925) — an in-silico prediction, not a clinical call.

ATOSB p.Arg490Gln

c.1469G>A · VCV3968499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0925 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00756%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0925	likely benign
REVEL	0.389	indeterminate
SaProt	LLR -6.65	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 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 1,348 bp · p 7.4e-07 · regional, not allelic
Overall
CADD	24.0	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 0.00756% European (non-Finnish) · 89/1,177,606 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0058%

Overall 0.00596% 96/1,610,100 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00756%	13,232
South Asian	0.0033%	30,279
Remaining individualsnot grpmax-eligible	0.00321%	31,125
East Asian	0.00223%	44,794
African / African-American	0.00134%	74,796

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.Arg490Gln
Coding: c.1469G>A
MANE Select: NM_025182
Type: single nucleotide variant
Location: chr9:35105369 (GRCh38)
Structure: AlphaFold pLDDT 56.25

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-arg490gln (accessed [today's date]).

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