Is CDKN1B p.Gln147Pro (c.440A>C) pathogenic?

CDKN1B p.Gln147Pro (c.440A>C) is classified Uncertain significance in CDKN1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-27). AlphaMissense: likely benign (0.0583); Absent from gnomAD v4.1; Associated with multiple endocrine neoplasia type 4.

What condition is associated with CDKN1B p.Gln147Pro (c.440A>C)?

CDKN1B p.Gln147Pro (c.440A>C) is associated with multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Gln147Pro (c.440A>C) in the general population?

CDKN1B p.Gln147Pro (c.440A>C) is absent from gnomAD v4.1 (gnomAD).

How is Multiple endocrine neoplasia type 4 inherited?

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

What do computational predictors say about CDKN1B p.Gln147Pro (c.440A>C)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

CDKN1B p.Gln147Pro

c.440A>C · rs1946499421 · VCV1718101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple endocrine neoplasia type 4

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -4.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.1, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 1,103 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	17.77	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: CDKN1B
Protein: p.Gln147Pro
Coding: c.440A>C
MANE Select: NM_004064
dbSNP: rs1946499421
Type: single nucleotide variant
Location: chr12:12718279 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 147: the 'disordered' region

Full CDKN1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multiple endocrine neoplasia type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple endocrine neoplasia type 4 (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult

Similar variants

CDKN1B p.Gln147= Likely benign ★★ same residue
CDKN1B p.Gln147Arg Uncertain significance ★ ⚠ same residue
CDKN1B p.Gln147His Uncertain significance ★ ⚠ same residue
CDKN1B p.Gln147Lys Uncertain significance ★ ⚠ same residue
CDKN1B p.Arg154Ter Pathogenic ★★ same condition
CDKN1B p.Arg5Ter Pathogenic/Likely pathogenic ★★ same condition
CDKN1B p.Gln104Ter Pathogenic ★★ same condition
CDKN1B p.Gln107Ter 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/cdkn1b-p-gln147pro (accessed [today's date]).

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