Is KRAS p.Tyr4Phe (c.11A>T) pathogenic?

KRAS p.Tyr4Phe (c.11A>T) is classified Uncertain significance in KRAS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-29). AlphaMissense: likely benign (0.3196); Absent from gnomAD v4.1; Associated with prostate cancer, hereditary, 1.

What condition is associated with KRAS p.Tyr4Phe (c.11A>T)?

KRAS p.Tyr4Phe (c.11A>T) is associated with prostate cancer, hereditary, 1 (ClinVar).

How common is KRAS p.Tyr4Phe (c.11A>T) in the general population?

KRAS p.Tyr4Phe (c.11A>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial prostate cancer inherited?

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

What do computational predictors say about KRAS p.Tyr4Phe (c.11A>T)?

AlphaMissense predicts likely benign (score 0.3196) — an in-silico prediction, not a clinical call.

KRAS p.Tyr4Phe

c.11A>T · rs2548933406 · VCV1711001

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3196 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

prostate cancer, hereditary, 1

Computational evidence

Protein change
AlphaMissense	0.3196	likely benign
REVEL	0.523	indeterminate
SaProt	LLR -12.48	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 20 kb · p 1.6e-16 · regional, not allelic
Overall
CADD	26.2	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.Tyr4Phe
Coding: c.11A>T
MANE Select: NM_004985
dbSNP: rs2548933406
Type: single nucleotide variant
Location: chr12:25245374 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 549 PDB
Residue 4: a β-strand

Full KRAS 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

KRAS p.Tyr4Asn Uncertain significance ⚠ same residue
KRAS p.Tyr4Ter Uncertain significance same residue
KRAS p.Tyr4fs Uncertain significance same residue
KRAS p.Asp30= Likely benign ★★★ same condition
KRAS p.Lys5Glu Pathogenic/Likely pathogenic ★★ same condition
KRAS c.111+16A>G Likely benign ★ same condition
KRAS p.Gln25= Likely benign ★ same condition
KRAS c.111+11T>C 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/kras-p-tyr4phe (accessed [today's date]).

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