Is CDKN1B p.Ser56= (c.168C>T) pathogenic?

CDKN1B p.Ser56= (c.168C>T) is classified Benign/Likely benign in CDKN1B (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.02%, eas); Associated with multiple endocrine neoplasia type 4.

What condition is associated with CDKN1B p.Ser56= (c.168C>T)?

CDKN1B p.Ser56= (c.168C>T) is associated with multiple endocrine neoplasia type 4, hereditary neoplastic syndrome (ClinVar).

How common is CDKN1B p.Ser56= (c.168C>T) in the general population?

CDKN1B p.Ser56= (c.168C>T) is ultra-rare (popmax 0.02%, eas) (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.Ser56=

c.168C>T · rs35456792 · VCV469002

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Conditions

multiple endocrine neoplasia type 4

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 2.1	GERP 0.62, phastCons 1
Overall
CADD	13.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% East Asian · 9/44,890 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00694% 112/1,614,078 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,988
European (non-Finnish)	0.0083%	12,041
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00267%	37,460

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.Ser56=
Coding: c.168C>T
MANE Select: NM_004064
dbSNP: rs35456792
Type: single nucleotide variant
Location: chr12:12718007 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 56: the 'interaction with cdk2' region; an α-helix

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

Also linked: hereditary neoplastic syndrome

For Multiple endocrine neoplasia type 4 (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult

Similar variants

CDKN1B p.Ser56Arg Uncertain significance ★★ ⚠ same residue
CDKN1B p.Ser56Thr Uncertain significance ★★ ⚠ same residue
CDKN1B p.Ser56Cys Uncertain significance ★ ⚠ same residue
CDKN1B p.Ser56fs 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-ser56 (accessed [today's date]).

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