Is CDKN1A p.Lys154= (c.462A>G) pathogenic?

CDKN1A p.Lys154= (c.462A>G) is classified Likely benign in CDKN1A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-01). Very rare (popmax 0.00127%, nfe).

How common is CDKN1A p.Lys154= (c.462A>G) in the general population?

CDKN1A p.Lys154= (c.462A>G) is very rare (popmax 0.00127%, nfe) (gnomAD).

CDKN1A p.Lys154=

c.462A>G · rs781057608 · VCV2656519

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP -3.9, phastCons 0.98
Overall
CADD	8.709	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,179,968 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00103% 15/1,461,864 alleles · very rare

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: CDKN1A
Protein: p.Lys154=
Coding: c.462A>G
MANE Select: NM_000389
dbSNP: rs781057608
Type: single nucleotide variant
Location: chr6:36685767 (GRCh38)
Gene constraint: LOEUF 1.492 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.16 · 13 PDB
Residue 154: a β-strand; the 'disordered' region; the 'interaction with trim39' region

Full CDKN1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN1A p.Arg84Gln Likely benign ★★ same type
CDKN1A p.Pro4= Benign/Likely benign ★★ same type
CDKN1A p.Ser31= Likely benign ★★ same type
CDKN1A p.Thr80= Likely benign ★★ same type
CDKN1A p.Ala106Val Uncertain significance ★ ⚠ same type
CDKN1A p.Arg20His Uncertain significance ★ ⚠ same type
CDKN1A p.Arg32His Uncertain significance ★ ⚠ same type
CDKN1A p.Arg46His 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/cdkn1a-p-lys154 (accessed [today's date]).

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