Is KRAS p.Asp154Val (c.461A>T) pathogenic?

KRAS p.Asp154Val (c.461A>T) is classified Uncertain significance in KRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-12). AlphaMissense: likely pathogenic (0.6269); Absent from gnomAD v4.1.

How common is KRAS p.Asp154Val (c.461A>T) in the general population?

KRAS p.Asp154Val (c.461A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRAS p.Asp154Val (c.461A>T)?

AlphaMissense predicts likely pathogenic (score 0.6269) — an in-silico prediction, not a clinical call.

KRAS p.Asp154Val

c.461A>T · rs989151052 · VCV2581679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6269 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6269	likely pathogenic
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -13.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.33	acceptor loss, 10 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 0.056 · regional, not allelic
Overall
CADD	22.7	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.Asp154Val
Coding: c.461A>T
MANE Select: NM_004985 · reported on NM_033360
dbSNP: rs989151052
Type: single nucleotide variant
Location: chr12:25215550 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 154: an α-helix

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

Similar variants

KRAS p.Asp154Gly Uncertain significance ★ ⚠ same residue
KRAS p.Asp154del Likely pathogenic ★ 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-asp154val (accessed [today's date]).

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