Is KRAS p.Val7Met (c.19G>A) pathogenic?

KRAS p.Val7Met (c.19G>A) is classified Uncertain significance in KRAS (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9941); Absent from gnomAD v4.1.

How common is KRAS p.Val7Met (c.19G>A) in the general population?

KRAS p.Val7Met (c.19G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRAS p.Val7Met (c.19G>A)?

AlphaMissense predicts likely pathogenic (score 0.9941) — an in-silico prediction, not a clinical call.

KRAS p.Val7Met

c.19G>A · rs2135806349 · VCV1049331

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9941	likely pathogenic
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -13.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 20 kb · p 1.6e-16 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Val7Met
Coding: c.19G>A
MANE Select: NM_004985
dbSNP: rs2135806349
Type: single nucleotide variant
Location: chr12:25245366 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 7: a β-strand

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

Similar variants

KRAS p.Val7Glu Likely pathogenic ★ same residue
KRAS p.Val7= Likely benign ★ same residue
KRAS p.Asp153Val Pathogenic ★★★ same type
KRAS p.Gln22Arg Pathogenic ★★★ same type
KRAS p.Gly60Arg Pathogenic ★★★ same type
KRAS p.Lys5Asn Pathogenic ★★★ same type
KRAS p.Pro34Leu Pathogenic ★★★ same type
KRAS p.Ser65Ile Likely 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/kras-p-val7met (accessed [today's date]).

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