Is NRAS p.Ala155= (c.465T>G) pathogenic?

NRAS p.Ala155= (c.465T>G) is classified Likely benign in NRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). Very rare (popmax 6.2e-05%); Associated with RASopathy.

What condition is associated with NRAS p.Ala155= (c.465T>G)?

NRAS p.Ala155= (c.465T>G) is associated with RASopathy (ClinVar).

How common is NRAS p.Ala155= (c.465T>G) in the general population?

NRAS p.Ala155= (c.465T>G) is very rare (popmax 6.2e-05%) (gnomAD).

NRAS p.Ala155=

c.465T>G · rs909184179 · VCV1582458

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

RASopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -2.1, phastCons 0.99
Overall
CADD	8.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,882 alleles · very rare exomes 1/1,461,542 · genomes 0/152,340 · joint denominator

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: NRAS
Protein: p.Ala155=
Coding: c.465T>G
MANE Select: NM_002524
dbSNP: rs909184179
Type: single nucleotide variant
Location: chr1:114708640 (GRCh38)
Gene constraint: LOEUF 0.55 · pLI 0.94 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.56 · 36 PDB
Residue 155: an α-helix

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

Disease context

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

Similar variants

NRAS p.Ala155Val Uncertain significance ★★ ⚠ same residue
NRAS p.Ala155Thr Uncertain significance ★ ⚠ same residue
NRAS p.Gly12Ser Pathogenic ★★★ same condition
NRAS p.Gly60Glu Pathogenic ★★★ same condition
NRAS p.Ile24Asn Likely pathogenic ★★★ same condition
NRAS p.Thr50Ile Pathogenic ★★★ same condition
NRAS p.Thr58Ile Pathogenic ★★★ same condition
NRAS p.Ala11Thr Uncertain significance ★★★ ⚠ 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-ala155 (accessed [today's date]).

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