Is HRAS p.Thr58= (c.174C>T) pathogenic?

HRAS p.Thr58= (c.174C>T) is classified Likely benign in HRAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-22). Very rare (popmax 0.00167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with HRAS p.Thr58= (c.174C>T)?

HRAS p.Thr58= (c.174C>T) is associated with Cardiovascular phenotype, Costello syndrome (ClinVar).

How common is HRAS p.Thr58= (c.174C>T) in the general population?

HRAS p.Thr58= (c.174C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

HRAS p.Thr58=

c.174C>T · rs746639086 · VCV697806

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Cardiovascular phenotype

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 -2.1	GERP -3.7
Overall
CADD	4.883	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,000 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00105% 17/1,613,166 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,472
African / African-American	0.00133%	74,912
European (non-Finnish)	0.00119%	84,284

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.Thr58=
Coding: c.174C>T
MANE Select: NM_198075 · reported on NM_005343
dbSNP: rs746639086
Type: single nucleotide variant
Location: chr11:533882 (GRCh38)

Full HRAS 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

Also linked: Costello syndrome

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-thr58 (accessed [today's date]).

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