Is ATOSA p.Ser869Arg (c.2605A>C) pathogenic?

ATOSA p.Ser869Arg (c.2605A>C) is classified Uncertain significance in ATOSA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). AlphaMissense: likely pathogenic (0.8814); Very rare (popmax 0.00134%, afr).

How common is ATOSA p.Ser869Arg (c.2605A>C) in the general population?

ATOSA p.Ser869Arg (c.2605A>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ATOSA p.Ser869Arg (c.2605A>C)?

AlphaMissense predicts likely pathogenic (score 0.8814) — an in-silico prediction, not a clinical call.

ATOSA p.Ser869Arg

c.2605A>C · VCV3803578

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8814 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8814	likely pathogenic · top 10% in ATOSA
REVEL	0.123	moderately benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 17 kb · p 0.027 · regional, not allelic
Overall
CADD	23.5	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 0.00134% African / African-American · 1/74,872 alleles

Overall 0.000657% 1/152,224 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: ATOSA
Protein: p.Ser869Arg
Coding: c.2605A>C
MANE Select: NM_001385016
Type: single nucleotide variant
Location: chr15:52600171 (GRCh38)
Structure: AlphaFold pLDDT 55.15

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

Similar variants

ATOSA p.Ser869Gly Uncertain significance ★ ⚠ same residue
ATOSA p.Ala116Val Uncertain significance ★ ⚠ same type
ATOSA p.Ala121Val Uncertain significance ★ ⚠ same type
ATOSA p.Ala294Gly Uncertain significance ★ ⚠ same type
ATOSA p.Ala375Pro Uncertain significance ★ ⚠ same type
ATOSA p.Arg1012Gln Uncertain significance ★ ⚠ same type
ATOSA p.Arg134Gln Uncertain significance ★ ⚠ same type
ATOSA p.Arg266Cys 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/atosa-p-ser869arg (accessed [today's date]).

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