Is HRAS p.Glu49fs (c.146del) pathogenic?

HRAS p.Glu49fs (c.146del) is classified Uncertain significance in HRAS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-29). Absent from gnomAD; Associated with prostate cancer, hereditary, 1.

What condition is associated with HRAS p.Glu49fs (c.146del)?

HRAS p.Glu49fs (c.146del) is associated with prostate cancer, hereditary, 1 (ClinVar).

How common is HRAS p.Glu49fs (c.146del) in the general population?

HRAS p.Glu49fs (c.146del) is absent from gnomAD (gnomAD).

How is Familial prostate cancer inherited?

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

HRAS p.Glu49fs

c.146del · rs2539798688 · VCV1711126

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

prostate cancer, hereditary, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP -3.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HRAS
Protein: p.Glu49fs
Coding: c.146del
MANE Select: NM_005343
dbSNP: rs2539798688
Type: Deletion
Location: chr11:533910 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.50 · 256 PDB
Residue 49: 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.Glu49= Likely benign ★★ same residue
HRAS p.Glu49Gln Uncertain significance ★ ⚠ same residue
HRAS p.Glu49Gly Uncertain significance ★ ⚠ same residue
HRAS p.Glu49Lys Uncertain significance ★ ⚠ same residue
HRAS p.Asp57Ala Uncertain significance ⚠ same condition
HRAS p.Met67Leu Uncertain significance ⚠ same condition
HRAS p.Thr50fs Uncertain significance same condition
HRAS p.Val81= 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-glu49fs (accessed [today's date]).

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