Is ATOSB p.Trp136Ser (c.407G>C) pathogenic?

ATOSB p.Trp136Ser (c.407G>C) is classified Uncertain significance in ATOSB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). AlphaMissense: likely benign (0.0774); Absent from gnomAD v4.1.

How common is ATOSB p.Trp136Ser (c.407G>C) in the general population?

ATOSB p.Trp136Ser (c.407G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATOSB p.Trp136Ser (c.407G>C)?

AlphaMissense predicts likely benign (score 0.0774) — an in-silico prediction, not a clinical call.

ATOSB p.Trp136Ser

c.407G>C · rs2490613247 · VCV2483764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0774 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0774	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -3.08	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 0.58	GERP 1.4, phastCons 0.48
Regional constraint	o/e 1.00	unconstrained · MANE · 1,701 bp · p 0.96 · regional, not allelic
Overall
CADD	19.64	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATOSB
Protein: p.Trp136Ser
Coding: c.407G>C
MANE Select: NM_025182
dbSNP: rs2490613247
Type: single nucleotide variant
Location: chr9:35107868 (GRCh38)
Structure: AlphaFold pLDDT 56.25
Residue 136: the 'disordered' region

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-trp136ser (accessed [today's date]).

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