Is DIRAS3 p.Arg18Gln (c.53G>A) pathogenic?

DIRAS3 p.Arg18Gln (c.53G>A) is classified Uncertain significance in DIRAS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). AlphaMissense: likely benign (0.1502); Absent from gnomAD v4.1.

How common is DIRAS3 p.Arg18Gln (c.53G>A) in the general population?

DIRAS3 p.Arg18Gln (c.53G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIRAS3 p.Arg18Gln (c.53G>A)?

AlphaMissense predicts likely benign (score 0.1502) — an in-silico prediction, not a clinical call.

DIRAS3 p.Arg18Gln

c.53G>A · VCV4011816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1502 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1502	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -6.79	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 0.038	GERP -1.6, phastCons 0.004
Regional constraint	o/e 0.83	unconstrained · MANE · 686 bp · p 0.0024 · regional, not allelic
Overall
CADD	8.106	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: DIRAS3
Protein: p.Arg18Gln
Coding: c.53G>A
MANE Select: NM_004675
Type: single nucleotide variant
Location: chr1:68047245 (GRCh38)
Gene constraint: LOEUF 1.84 · pLI 0.34 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.19 · 1 PDB

Full DIRAS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIRAS3 p.Arg18Trp Uncertain significance ★ ⚠ same residue
DIRAS3 p.Ala129Thr Uncertain significance ★ ⚠ same type
DIRAS3 p.Arg27Gly Uncertain significance ★ ⚠ same type
DIRAS3 p.Arg99Leu Uncertain significance ★ ⚠ same type
DIRAS3 p.Asn174His Uncertain significance ★ ⚠ same type
DIRAS3 p.Asn217Ser Uncertain significance ★ ⚠ same type
DIRAS3 p.Gln102Arg Uncertain significance ★ ⚠ same type
DIRAS3 p.Gln76Ter 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/diras3-p-arg18gln (accessed [today's date]).

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