Is DIRAS1 p.Val11Met (c.31G>A) pathogenic?

DIRAS1 p.Val11Met (c.31G>A) is classified Uncertain significance in DIRAS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely pathogenic (0.9562); Very rare (popmax 0.000138%).

How common is DIRAS1 p.Val11Met (c.31G>A) in the general population?

DIRAS1 p.Val11Met (c.31G>A) is very rare (popmax 0.000138%) (gnomAD).

What do computational predictors say about DIRAS1 p.Val11Met (c.31G>A)?

AlphaMissense predicts likely pathogenic (score 0.9562) — an in-silico prediction, not a clinical call.

DIRAS1 p.Val11Met

c.31G>A · rs1389642131 · VCV3082539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9562 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000138%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9562	likely pathogenic
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -9.92	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 426 bp · p 6.7e-08 · regional, not allelic
Overall
CADD	33.0	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 0.000138%

Overall 0.000138% 2/1,449,232 alleles · very 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: DIRAS1
Protein: p.Val11Met
Coding: c.31G>A
MANE Select: NM_145173
dbSNP: rs1389642131
Type: single nucleotide variant
Location: chr19:2717776 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI 0.35 (gnomAD)
Structure: AlphaFold pLDDT 87.01 · 1 PDB
Residue 11: a β-strand

Full DIRAS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIRAS1 p.Ala145Ser Uncertain significance ★ ⚠ same type
DIRAS1 p.Arg181Gly Uncertain significance ★ ⚠ same type
DIRAS1 p.Arg190Gly Uncertain significance ★ ⚠ same type
DIRAS1 p.Arg190His Uncertain significance ★ ⚠ same type
DIRAS1 p.Asp113Asn Uncertain significance ★ ⚠ same type
DIRAS1 p.Asp178Glu Uncertain significance ★ ⚠ same type
DIRAS1 p.Glu41Lys Uncertain significance ★ ⚠ same type
DIRAS1 p.Gly109Ala 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/diras1-p-val11met (accessed [today's date]).

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