Is HRAS p.Asn86= (c.258C>T) pathogenic?

HRAS p.Asn86= (c.258C>T) is classified Likely benign in HRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). Very rare (popmax 0.00667%, afr); Associated with Costello syndrome.

What condition is associated with HRAS p.Asn86= (c.258C>T)?

HRAS p.Asn86= (c.258C>T) is associated with Costello syndrome (ClinVar).

How common is HRAS p.Asn86= (c.258C>T) in the general population?

HRAS p.Asn86= (c.258C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

HRAS p.Asn86=

c.258C>T · rs765849763 · VCV1121809

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Conditions

Costello syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.41	GERP -3.7, phastCons 0.98
Overall
CADD	3.548	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,928 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00031% 5/1,613,306 alleles · very rare

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: HRAS
Protein: p.Asn86=
Coding: c.258C>T
MANE Select: NM_198075 · reported on NM_005343
dbSNP: rs765849763
Type: single nucleotide variant
Location: chr11:533798 (GRCh38)

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

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-asn86 (accessed [today's date]).

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