Is ATOSA p.Phe12Val (c.34T>G) pathogenic?

ATOSA p.Phe12Val (c.34T>G) is classified Uncertain significance in ATOSA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely pathogenic (0.6956); Very rare (popmax 0.00133%, afr).

How common is ATOSA p.Phe12Val (c.34T>G) in the general population?

ATOSA p.Phe12Val (c.34T>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ATOSA p.Phe12Val (c.34T>G)?

AlphaMissense predicts likely pathogenic (score 0.6956) — an in-silico prediction, not a clinical call.

ATOSA p.Phe12Val

c.34T>G · VCV3327136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6956 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6956	likely pathogenic
REVEL	0.415	indeterminate
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 64 kb · p 0.61 · regional, not allelic
Overall
CADD	26.3	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 0.00133% African / African-American · 1/74,932 alleles

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

Overall 0.000372% 6/1,613,624 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,231
African / African-Americangrpmax	0.00133%	74,932
European (non-Finnish)	0.000254%	393,253

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe12Val
Coding: c.34T>G
MANE Select: NM_001385016
Type: single nucleotide variant
Location: chr15:52613840 (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-phe12val (accessed [today's date]).

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