Is ATOSB p.Arg68Leu (c.203G>T) pathogenic?

ATOSB p.Arg68Leu (c.203G>T) is classified Uncertain significance in ATOSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: likely benign (0.1994); Rare (popmax 0.205%, eas).

How common is ATOSB p.Arg68Leu (c.203G>T) in the general population?

ATOSB p.Arg68Leu (c.203G>T) is rare (popmax 0.205%, eas) (gnomAD).

What do computational predictors say about ATOSB p.Arg68Leu (c.203G>T)?

AlphaMissense predicts likely benign (score 0.1994) — an in-silico prediction, not a clinical call.

ATOSB p.Arg68Leu

c.203G>T · VCV3968509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1994 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.205%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1994	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -10.72	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,701 bp · p 0.96 · regional, not allelic
Overall
CADD	23.1	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 0.205% East Asian · 90/43,964 alleles

Filtering AF 0.171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.158%

Overall 0.00587% 90/1,534,226 alleles · 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: ATOSB
Protein: p.Arg68Leu
Coding: c.203G>T
MANE Select: NM_025182
Type: single nucleotide variant
Location: chr9:35108072 (GRCh38)
Structure: AlphaFold pLDDT 56.25
Residue 68: 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-arg68leu (accessed [today's date]).

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