Is ATAT1 p.Arg293His (c.878G>A) pathogenic?

ATAT1 p.Arg293His (c.878G>A) is classified Uncertain significance in ATAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.2241); Very rare (popmax 0.00223%, eas).

How common is ATAT1 p.Arg293His (c.878G>A) in the general population?

ATAT1 p.Arg293His (c.878G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ATAT1 p.Arg293His (c.878G>A)?

AlphaMissense predicts likely benign (score 0.2241) — an in-silico prediction, not a clinical call.

ATAT1 p.Arg293His

c.878G>A · VCV3959464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2241 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2241	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -7.74	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 12	phastCons 1
Overall
CADD	31.0	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 0.00223% East Asian · 1/44,750 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000744% 12/1,612,234 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,750
South Asian	0.0011%	91,004
European (non-Finnish)	0.000848%	117,975

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: ATAT1
Protein: p.Arg293His
Coding: c.878G>A
MANE Select: NM_001413067
Type: single nucleotide variant
Location: chr6:30642921 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.28 · 10 PDB

Full ATAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATAT1 c.107+217G>T Uncertain significance ★ same type
ATAT1 p.Ala203Glu Uncertain significance ★ ⚠ same type
ATAT1 p.Ala304Thr Uncertain significance ★ ⚠ same type
ATAT1 p.Arg158Gln Uncertain significance ★ ⚠ same type
ATAT1 p.Arg205Gln Uncertain significance ★ ⚠ same type
ATAT1 p.Arg269Cys Uncertain significance ★ ⚠ same type
ATAT1 p.Arg269Gly Uncertain significance ★ ⚠ same type
ATAT1 p.Arg269His 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/atat1-p-arg293his (accessed [today's date]).

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