Is HRAS p.Asp105= (c.315C>T) pathogenic?

HRAS p.Asp105= (c.315C>T) is classified Likely benign in HRAS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-01). Very rare (popmax 0.00167%, amr); Associated with Costello syndrome.

What condition is associated with HRAS p.Asp105= (c.315C>T)?

HRAS p.Asp105= (c.315C>T) is associated with Costello syndrome (ClinVar).

How common is HRAS p.Asp105= (c.315C>T) in the general population?

HRAS p.Asp105= (c.315C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

HRAS p.Asp105=

c.315C>T · rs1229925274 · VCV1649504

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 4.2	GERP -3.7, phastCons 1
Overall
CADD	4.146	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,028 alleles

Overall 0.000124% 2/1,613,882 alleles · very rare exomes 2/1,461,540 · genomes 0/152,342 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,028
European (non-Finnish)	8.47e-05%	1,179,993

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.Asp105=
Coding: c.315C>T
MANE Select: NM_005343
dbSNP: rs1229925274
Type: single nucleotide variant
Location: chr11:533588 (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-asp105 (accessed [today's date]).

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