Is DIRAS2 p.Glu190Asp (c.570G>T) pathogenic?

DIRAS2 p.Glu190Asp (c.570G>T) is classified Uncertain significance in DIRAS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely benign (0.0941); Very rare (popmax 0.00203%, nfe).

How common is DIRAS2 p.Glu190Asp (c.570G>T) in the general population?

DIRAS2 p.Glu190Asp (c.570G>T) is very rare (popmax 0.00203%, nfe) (gnomAD).

What do computational predictors say about DIRAS2 p.Glu190Asp (c.570G>T)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

DIRAS2 p.Glu190Asp

c.570G>T · rs370332203 · VCV2333913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -6.62	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 -0.32	GERP -5.1, phastCons 0.18
Regional constraint	o/e 0.73	unconstrained · MANE · 596 bp · p 9e-06 · regional, not allelic
Overall
CADD	12.52	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 0.00203% European (non-Finnish) · 24/1,180,006 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00155% 25/1,613,828 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,167
African / African-American	0.00134%	74,886

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: DIRAS2
Protein: p.Glu190Asp
Coding: c.570G>T
MANE Select: NM_017594
dbSNP: rs370332203
Type: single nucleotide variant
Location: chr9:90613258 (GRCh38)
Gene constraint: LOEUF 0.782 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 88.69 · 2 PDB

Full DIRAS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIRAS2 p.Ala138= Benign ★★ same type
DIRAS2 p.Asp51= Benign ★★ same type
DIRAS2 p.Ala146Thr Uncertain significance ★ ⚠ same type
DIRAS2 p.Arg73Gln Uncertain significance ★ ⚠ same type
DIRAS2 p.Gln177Arg Uncertain significance ★ ⚠ same type
DIRAS2 p.Ile88Val Uncertain significance ★ ⚠ same type
DIRAS2 p.Pro127Leu Uncertain significance ★ ⚠ same type
DIRAS2 p.Ser53Asn 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/diras2-p-glu190asp (accessed [today's date]).

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