Is HRAS p.Val81= (c.243G>T) pathogenic?

HRAS p.Val81= (c.243G>T) is classified Uncertain significance in HRAS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-29). Absent from gnomAD v4.1; Associated with prostate cancer, hereditary, 1.

What condition is associated with HRAS p.Val81= (c.243G>T)?

HRAS p.Val81= (c.243G>T) is associated with prostate cancer, hereditary, 1 (ClinVar).

How common is HRAS p.Val81= (c.243G>T) in the general population?

HRAS p.Val81= (c.243G>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial prostate cancer inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

HRAS p.Val81=

c.243G>T · rs2133990247 · VCV1711129

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

prostate cancer, hereditary, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.66	GERP -3.7, phastCons 0.026
Overall
CADD	1.997	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HRAS
Protein: p.Val81=
Coding: c.243G>T
MANE Select: NM_005343
dbSNP: rs2133990247
Type: single nucleotide variant
Location: chr11:533813 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.50 · 256 PDB
Residue 81: a β-strand

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

Disease context

prostate cancer, hereditary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial prostate cancer (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

HRAS p.Asp57Ala Uncertain significance ⚠ same condition
HRAS p.Met67Leu Uncertain significance ⚠ same condition
HRAS p.Glu49fs Uncertain significance same condition
HRAS p.Thr50fs Uncertain significance same condition
HRAS p.Ala59Thr Likely pathogenic ★★★ same type
HRAS p.Gly12Ser Pathogenic ★★★ same type
HRAS p.Gly13Cys Pathogenic ★★★ same type
HRAS p.Lys117Arg Pathogenic ★★★ same type

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-val81 (accessed [today's date]).

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