Is KRAS p.Pro34Gln (c.101C>A) pathogenic?

KRAS p.Pro34Gln (c.101C>A) is classified Likely pathogenic in KRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1; Associated with KRAS-related disorder.

What condition is associated with KRAS p.Pro34Gln (c.101C>A)?

KRAS p.Pro34Gln (c.101C>A) is associated with KRAS-related disorder (ClinVar).

How common is KRAS p.Pro34Gln (c.101C>A) in the general population?

KRAS p.Pro34Gln (c.101C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRAS p.Pro34Gln (c.101C>A)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

KRAS p.Pro34Gln

c.101C>A · rs104894366 · VCV2630513

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KRAS-related disorder

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 3% in KRAS
REVEL	0.899	moderately pathogenic-leaning
SaProt	LLR -15.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 20 kb · p 1.6e-16 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: KRAS
Protein: p.Pro34Gln
Coding: c.101C>A
MANE Select: NM_004985
dbSNP: rs104894366
Type: single nucleotide variant
Location: chr12:25245284 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 34: a UniProt-annotated variant site (in ns3; characterized by a defective gtpase-activating protein sensitivity and a strongly reduced interaction with effectors); a UniProt-annotated variant site (in ns3); a UniProt-annotated variant site (in cfc2; characterized by a defective gtpase-activating protein sensitivity and a strongly reduced interaction with effectors); an α-helix

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

Disease context

KRAS-related disorder

Similar variants

KRAS p.Pro34Leu Pathogenic ★★★ same residue
KRAS p.Pro34Arg Pathogenic/Likely pathogenic ★★ same residue
KRAS p.Pro34= Likely benign ★ same residue
KRAS c.*22C>G Pathogenic ★★ same condition
KRAS p.Ala59Ser Pathogenic/Likely pathogenic ★★ same condition
KRAS p.Asp153Gly Pathogenic/Likely pathogenic ★★ same condition
KRAS p.Gln22Glu Pathogenic ★★ same condition
KRAS p.Gln22Lys Pathogenic/Likely pathogenic ★★ 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/kras-p-pro34gln (accessed [today's date]).

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