Is NRAS p.Gln61Arg (c.182A>G) pathogenic?

NRAS p.Gln61Arg (c.182A>G) is classified Pathogenic in NRAS (ClinVar, Multiple submitters, 14 submitters; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.9912); Absent from gnomAD v4.1; Associated with vascular malformation.

What condition is associated with NRAS p.Gln61Arg (c.182A>G)?

NRAS p.Gln61Arg (c.182A>G) is associated with vascular malformation, non-small cell lung carcinoma, colorectal cancer (ClinVar).

How common is NRAS p.Gln61Arg (c.182A>G) in the general population?

NRAS p.Gln61Arg (c.182A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NRAS p.Gln61Arg (c.182A>G)?

AlphaMissense predicts likely pathogenic (score 0.9912) — an in-silico prediction, not a clinical call.

NRAS p.Gln61Arg

c.182A>G · rs11554290 · VCV13900

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely pathogenic

0.9912 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

vascular malformation

Computational evidence

Protein change
AlphaMissense	0.9912	likely pathogenic ✓ concordant with ClinVar
REVEL	0.888	moderately pathogenic-leaning
SaProt	LLR -12.43	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 7,622 bp · p 6.3e-09 · regional, not allelic
Overall
CADD	25.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Melanoma		B	Positive
Skin Melanoma	Binimetinib	B	Sensitivity/Response
Colorectal Cancer	Cetuximab	B	Resistance
Melanoma	Vemurafenib	B	Resistance
Skin Melanoma	Selumetinib	C	Sensitivity/Response
Colorectal Cancer	Cetuximab,Chemotherapy	B	Resistance
Follicular Thyroid Carcinoma		B
Follicular Thyroid Carcinoma		B	Poor Outcome

Variant & gene context

Gene: NRAS
Protein: p.Gln61Arg
Coding: c.182A>G
MANE Select: NM_002524
dbSNP: rs11554290
Type: single nucleotide variant
Location: chr1:114713908 (GRCh38)
Gene constraint: LOEUF 0.55 · pLI 0.94 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.56 · 36 PDB
Residue 61: a UniProt-annotated variant site (in cmns and ncms; somatic mutation); a UniProt-annotated variant site (in cmns, ncms, knen and nmtc2; also found in lung carcinoma cell and melanoma; impaired gtp hydrolysis activity, trapping nras in a constitutive gtp-bound active conformation; promotes melanomagenesis; promotes interaction with shoc2 and pp1c); a binding site

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

Disease context

vascular malformation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: non-small cell lung carcinoma colorectal cancer nevus, epidermal linear nevus sebaceous syndrome thyroid cancer, nonmedullary, 2 neurocutaneous melanocytosis Noonan syndrome 6 large congenital melanocytic nevus

Similar variants

NRAS p.Gln61Pro Pathogenic ★ same residue
NRAS p.Gln61Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
NRAS p.Gln61Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
NRAS p.Gln61His Conflicting classifications of pathogenicity ★ ⚠ same residue
NRAS p.Gln61= Likely benign ★ same residue
NRAS p.Gly12Ser Pathogenic ★★★ same condition
NRAS p.Gly60Glu Pathogenic ★★★ same condition
NRAS p.Thr50Ile Pathogenic ★★★ ⚠ same condition

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/nras-p-gln61arg (accessed [today's date]).

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