Is CDKN1B p.Val6fs (c.15_16dup) pathogenic?

CDKN1B p.Val6fs (c.1516dup) is classified Pathogenic in CDKN1B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-08). No gnomAD frequency available for this variant; Associated with multiple endocrine neoplasia type 4.

What condition is associated with CDKN1B p.Val6fs (c.15_16dup)?

CDKN1B p.Val6fs (c.15_16dup) is associated with multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Val6fs (c.15_16dup) in the general population?

CDKN1B p.Val6fs (c.15_16dup) is no gnomAD frequency available for this variant (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.Val6fs

c.15_16dup · rs2136355351 · VCV1072930

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

multiple endocrine neoplasia type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -2.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDKN1B
Protein: p.Val6fs
Coding: c.15_16dup
MANE Select: NM_004064
dbSNP: rs2136355351
Type: Duplication
Location: chr12:12717852 (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.Val6Ala 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

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-val6fs (accessed [today's date]).

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