Is CDKN1B p.Val6Ala (c.17T>C) pathogenic?

CDKN1B p.Val6Ala (c.17T>C) is classified Uncertain significance in CDKN1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). AlphaMissense: likely pathogenic (0.8428); Absent from gnomAD v4.1; Associated with multiple endocrine neoplasia type 4.

What condition is associated with CDKN1B p.Val6Ala (c.17T>C)?

CDKN1B p.Val6Ala (c.17T>C) is associated with multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Val6Ala (c.17T>C) in the general population?

CDKN1B p.Val6Ala (c.17T>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.Val6Ala (c.17T>C)?

AlphaMissense predicts likely pathogenic (score 0.8428) — an in-silico prediction, not a clinical call.

CDKN1B p.Val6Ala

c.17T>C · rs1946485641 · VCV853264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8428 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

multiple endocrine neoplasia type 4

Computational evidence

Protein change
AlphaMissense	0.8428	likely pathogenic
REVEL	0.314	indeterminate
SaProt	LLR -2.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 1,103 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	24.1	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: CDKN1B
Protein: p.Val6Ala
Coding: c.17T>C
MANE Select: NM_004064
dbSNP: rs1946485641
Type: single nucleotide variant
Location: chr12:12717856 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 6: 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.Val6Leu Uncertain significance ★★ ⚠ same residue
CDKN1B p.Val6Met Uncertain significance ★★ ⚠ same residue
CDKN1B p.Val6= Likely benign ★★ same residue
CDKN1B p.Val6fs Pathogenic ★ 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-val6ala (accessed [today's date]).

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