Is ATOSA p.Arg69Cys (c.205C>T) pathogenic?

ATOSA p.Arg69Cys (c.205C>T) is classified Uncertain significance in ATOSA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.2113); Ultra-rare (popmax 0.0668%, amr).

How common is ATOSA p.Arg69Cys (c.205C>T) in the general population?

ATOSA p.Arg69Cys (c.205C>T) is ultra-rare (popmax 0.0668%, amr) (gnomAD).

What do computational predictors say about ATOSA p.Arg69Cys (c.205C>T)?

AlphaMissense predicts likely benign (score 0.2113) — an in-silico prediction, not a clinical call.

ATOSA p.Arg69Cys

c.205C>T · rs778671188 · VCV3131159

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2113 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0668%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2113	likely benign
REVEL	0.454	indeterminate
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.98 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 2,493 bp · p 0.55 · regional, not allelic
Overall
CADD	28.2	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 0.0668% Admixed American · 40/59,854 alleles

Filtering AF 0.0504% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0447%

Overall 0.00397% 64/1,612,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0668%	1,496
Remaining individualsnot grpmax-eligible	0.0032%	31,224
European (non-Finnish)	0.00178%	56,175
South Asian	0.0011%	90,718

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.Arg69Cys
Coding: c.205C>T
MANE Select: NM_001385016
dbSNP: rs778671188
Type: single nucleotide variant
Location: chr15:52611774 (GRCh38)
Structure: AlphaFold pLDDT 55.15

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

Similar variants

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
ATOSA p.Arg266His 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-arg69cys (accessed [today's date]).

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