Is NRAS p.Ile84= (c.252C>T) pathogenic?

NRAS p.Ile84= (c.252C>T) is classified Likely benign in NRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-19). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with NRAS p.Ile84= (c.252C>T)?

NRAS p.Ile84= (c.252C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is NRAS p.Ile84= (c.252C>T) in the general population?

NRAS p.Ile84= (c.252C>T) is absent from gnomAD v4.1 (gnomAD).

NRAS p.Ile84=

c.252C>T · rs1365997556 · VCV1792664

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

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 8.4	GERP 0.84, phastCons 1
Overall
CADD	12.49	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.Ile84=
Coding: c.252C>T
MANE Select: NM_002524
dbSNP: rs1365997556
Type: single nucleotide variant
Location: chr1:114713838 (GRCh38)
Gene constraint: LOEUF 0.55 · pLI 0.94 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.56 · 36 PDB

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

Disease context

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

Similar variants

NRAS p.Ile84Val Uncertain significance ★★★ ⚠ same residue
NRAS p.Cys181Phe Uncertain significance ★★ ⚠ same condition
NRAS p.Gln129Glu Uncertain significance ★★ ⚠ same condition
NRAS p.Gly138Arg Uncertain significance ★★ ⚠ same condition
NRAS p.Ile36Thr Uncertain significance ★★ ⚠ same condition
NRAS p.Leu52Met Uncertain significance ★★ same condition
NRAS p.Thr127Arg Uncertain significance ★★ ⚠ same condition
NRAS p.Asp105= Likely benign ★★ 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-ile84 (accessed [today's date]).

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