Is HRAS p.Gln22Ter (c.64C>T) pathogenic?

HRAS p.Gln22Ter (c.64C>T) is classified Likely benign in HRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-30). Very rare (popmax 0.0011%, sas).

How common is HRAS p.Gln22Ter (c.64C>T) in the general population?

HRAS p.Gln22Ter (c.64C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

HRAS p.Gln22Ter

c.64C>T · rs121917757 · VCV279996

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,360 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,084
European (non-Finnish)	0.000509%	196,649

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.Gln22Ter
Coding: c.64C>T
MANE Select: NM_005343
dbSNP: rs121917757
Type: single nucleotide variant
Location: chr11:534259 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.50 · 256 PDB
Residue 22: a UniProt-annotated variant site (in cmems); an α-helix

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

Similar variants

HRAS p.Gln22Lys Pathogenic/Likely pathogenic ★★ same residue
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
HRAS p.Thr58Ile Pathogenic ★★★ same type
HRAS p.Gly138Ser Uncertain significance ★★★ ⚠ same type
HRAS p.Ile93Val Uncertain significance ★★★ ⚠ 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-gln22ter (accessed [today's date]).

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