Is CDKN1B p.Ter199= (c.*1dup) pathogenic?

CDKN1B p.Ter199= (c.1dup) is classified Uncertain significance in CDKN1B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-13). Very rare (popmax 8.47e-05%, nfe); Associated with multiple endocrine neoplasia type 4.

What condition is associated with CDKN1B p.Ter199= (c.*1dup)?

CDKN1B p.Ter199= (c.*1dup) is associated with multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Ter199= (c.*1dup) in the general population?

CDKN1B p.Ter199= (c.*1dup) is very rare (popmax 8.47e-05%, nfe) (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.

CDKN1B p.Ter199=

c.*1dup · rs2136357503 · VCV1502282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

multiple endocrine neoplasia type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 6.2e-05% 1/1,613,944 alleles · very rare exomes 1/1,461,686 · genomes 0/152,258 · joint denominator

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: CDKN1B
Protein: p.Ter199=
Coding: c.*1dup
MANE Select: NM_004064
dbSNP: rs2136357503
Type: Duplication
Location: chr12:12718944 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB

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.Ter199Tyr Uncertain significance ★ same residue
CDKN1B p.Ter199ValextTer? Uncertain significance ★ same residue
CDKN1B p.Asn8Ter Pathogenic/Likely pathogenic ★★ same condition
CDKN1B p.Gln104fs Pathogenic ★★ same condition
CDKN1B p.Glu126Ter Pathogenic ★★ same condition
CDKN1B p.Lys96fs Pathogenic/Likely pathogenic ★★ same condition
CDKN1B p.Gly192fs Uncertain significance ★★ same condition
CDKN1B p.Ala123fs 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-ter199 (accessed [today's date]).

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