Is RRAS2 p.Arg63Gln (c.188G>A) pathogenic?

RRAS2 p.Arg63Gln (c.188G>A) is classified Uncertain significance in RRAS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-06). AlphaMissense: ambiguous (0.4083); Very rare (popmax 0.00224%, sas).

How common is RRAS2 p.Arg63Gln (c.188G>A) in the general population?

RRAS2 p.Arg63Gln (c.188G>A) is very rare (popmax 0.00224%, sas) (gnomAD).

What do computational predictors say about RRAS2 p.Arg63Gln (c.188G>A)?

AlphaMissense predicts ambiguous (score 0.4083) — an in-silico prediction, not a clinical call.

RRAS2 p.Arg63Gln

c.188G>A · rs782597266 · VCV2959205

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4083 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, sas)

Computational evidence

Protein change
AlphaMissense	0.4083	ambiguous
REVEL	0.342	indeterminate
SaProt	LLR -4.50	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 80 kb · p 1e-06 · regional, not allelic
Overall
CADD	32.0	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 0.00224% South Asian · 2/89,332 alleles

Filtering AF 0.000372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000139%

Overall 0.00056% 9/1,605,824 alleles · very rare exomes 9/1,453,762 · genomes 0/152,062 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00224%	44,666
Remaining individualsnot grpmax-eligible	0.00161%	62,058
European (non-Finnish)	0.00051%	195,936

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: RRAS2
Protein: p.Arg63Gln
Coding: c.188G>A
MANE Select: NM_012250
dbSNP: rs782597266
Type: single nucleotide variant
Location: chr11:14295776 (GRCh38)
Gene constraint: LOEUF 1.246 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 3 PDB
Residue 63: a β-strand

Full RRAS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RRAS2 p.Ala70Thr Likely pathogenic ★★★ same type
RRAS2 p.Gln72Leu Pathogenic ★★★ same type
RRAS2 c.409-16A>T Benign ★★★ same type
RRAS2 p.Arg147Gln Uncertain significance ★★ ⚠ same type
RRAS2 p.Arg191Trp Uncertain significance ★★ ⚠ same type
RRAS2 p.Lys150Thr Uncertain significance ★★ ⚠ same type
RRAS2 p.Pro45Ala Uncertain significance ★★ ⚠ same type
RRAS2 p.Thr41Met 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/rras2-p-arg63gln (accessed [today's date]).

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