Is HRAS p.Tyr96= (c.288C>T) pathogenic?

HRAS p.Tyr96= (c.288C>T) is classified Likely benign in HRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). Very rare (popmax 0.00267%, afr); Associated with Costello syndrome.

What condition is associated with HRAS p.Tyr96= (c.288C>T)?

HRAS p.Tyr96= (c.288C>T) is associated with Costello syndrome (ClinVar).

How common is HRAS p.Tyr96= (c.288C>T) in the general population?

HRAS p.Tyr96= (c.288C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

HRAS p.Tyr96=

c.288C>T · rs367794954 · VCV1117140

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Costello syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	donor gain · deltas
Pangolin	Δ0.31	loss · gain 0.24 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 1.7	GERP -2.8, phastCons 1
Overall
CADD	17.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,918 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,613,216 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,459
European (non-Finnish)	0.000169%	590,005

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.Tyr96=
Coding: c.288C>T
MANE Select: NM_005343
dbSNP: rs367794954
Type: single nucleotide variant
Location: chr11:533768 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.50 · 256 PDB
Residue 96: an α-helix

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.Ala59Thr Likely pathogenic ★★★ same condition
HRAS p.Gly12Ser Pathogenic ★★★ same condition
HRAS p.Gly13Cys Pathogenic ★★★ same condition
HRAS p.Lys117Arg Pathogenic ★★★ same condition
HRAS p.Thr58Ile Pathogenic ★★★ same condition
HRAS p.Gly138Ser Uncertain significance ★★★ ⚠ same condition
HRAS p.Ile93Val Uncertain significance ★★★ ⚠ same condition
HRAS p.Lys170Ter 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-tyr96 (accessed [today's date]).

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