Is ATOSA p.Ser347Cys (c.1040C>G) pathogenic?

ATOSA p.Ser347Cys (c.1040C>G) is classified Uncertain significance in ATOSA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely benign (0.0789); Ultra-rare (popmax 0.0602%, eas).

How common is ATOSA p.Ser347Cys (c.1040C>G) in the general population?

ATOSA p.Ser347Cys (c.1040C>G) is ultra-rare (popmax 0.0602%, eas) (gnomAD).

What do computational predictors say about ATOSA p.Ser347Cys (c.1040C>G)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

ATOSA p.Ser347Cys

c.1040C>G · rs372900453 · VCV3131140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0602%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.1, phastCons 0.95
Regional constraint	o/e 1.08	unconstrained · MANE · 17 kb · p 0.027 · regional, not allelic
Overall
CADD	20.4	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 0.0602% East Asian · 27/44,868 alleles

Filtering AF 0.0424% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.00297% 48/1,613,546 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0602%	1,662
Remaining individualsnot grpmax-eligible	0.0128%	7,809
African / African-American	0.00799%	12,509
Admixed American	0.00501%	19,972
South Asian	0.0022%	45,523
European (non-Finnish)	0.00017%	589,828

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.Ser347Cys
Coding: c.1040C>G
MANE Select: NM_001385016
dbSNP: rs372900453
Type: single nucleotide variant
Location: chr15:52609874 (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-ser347cys (accessed [today's date]).

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