Is HRAS p.Ile142del (c.424_426del) pathogenic?

HRAS p.Ile142del (c.424426del) is classified Uncertain significance in HRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-28). Absent from gnomAD; Associated with Costello syndrome.

What condition is associated with HRAS p.Ile142del (c.424_426del)?

HRAS p.Ile142del (c.424_426del) is associated with Costello syndrome (ClinVar).

How common is HRAS p.Ile142del (c.424_426del) in the general population?

HRAS p.Ile142del (c.424_426del) is absent from gnomAD (gnomAD).

HRAS p.Ile142del

c.424_426del · rs2539791458 · VCV2737254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Costello syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HRAS
Protein: p.Ile142del
Coding: c.424_426del
MANE Select: NM_005343
dbSNP: rs2539791458
Type: Deletion
Location: chr11:533477 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.50 · 256 PDB
Residue 142: a β-strand

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

Disease context

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

Similar variants

HRAS p.Ile142Leu Uncertain significance ★★ ⚠ same residue
HRAS p.Ile142Met Uncertain significance ★★ ⚠ same residue
HRAS p.Ile142Phe Uncertain significance ★ ⚠ same residue
HRAS p.Ile142Thr Uncertain significance ★ ⚠ same residue
HRAS p.Ile142Val Uncertain significance ★ ⚠ same residue
HRAS p.Ile142= Likely benign ★ same residue
HRAS p.Leu163fs Pathogenic/Likely pathogenic ★★ same condition
HRAS p.Gly60fs 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/hras-p-ile142del (accessed [today's date]).

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