Is NRAS p.Lys147= (c.441G>A) pathogenic?

NRAS p.Lys147= (c.441G>A) is classified Likely benign in NRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). Absent from gnomAD v4.1; Associated with RASopathy.

What condition is associated with NRAS p.Lys147= (c.441G>A)?

NRAS p.Lys147= (c.441G>A) is associated with RASopathy (ClinVar).

How common is NRAS p.Lys147= (c.441G>A) in the general population?

NRAS p.Lys147= (c.441G>A) is absent from gnomAD v4.1 (gnomAD).

NRAS p.Lys147=

c.441G>A · VCV3721459

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 3.3	GERP 1.6, phastCons 1
Overall
CADD	12.37	PHRED · no single calibrated threshold — expert panels disagree

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.

Variant & gene context

Gene: NRAS
Protein: p.Lys147=
Coding: c.441G>A
MANE Select: NM_002524
Type: single nucleotide variant
Location: chr1:114709578 (GRCh38)
Gene constraint: LOEUF 0.55 · pLI 0.94 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.56 · 36 PDB
Residue 147: a turn

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.Lys147Asn 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
NRAS p.Ala91Val 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-lys147 (accessed [today's date]).

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