Is CDKN1B p.Ser12= (c.36C>T) pathogenic?

CDKN1B p.Ser12= (c.36C>T) is classified Likely benign in CDKN1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-31). Ultra-rare (popmax 0.011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Ser12= (c.36C>T)?

CDKN1B p.Ser12= (c.36C>T) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Ser12= (c.36C>T) in the general population?

CDKN1B p.Ser12= (c.36C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

CDKN1B p.Ser12=

c.36C>T · rs778425357 · VCV772559

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.7	GERP 0.49, phastCons 1
Overall
CADD	14.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,084 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00062% 10/1,613,876 alleles · ultra-rare exomes 10/1,461,568 · genomes 0/152,308 · 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.Ser12=
Coding: c.36C>T
MANE Select: NM_004064
dbSNP: rs778425357
Type: single nucleotide variant
Location: chr12:12717875 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 12: the 'disordered' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple endocrine neoplasia type 4

Similar variants

CDKN1B p.Ser12Asn Uncertain significance ★★ ⚠ same residue
CDKN1B p.Ser12Gly Uncertain significance ★★ ⚠ same residue
CDKN1B p.Ser12Thr Uncertain significance ★★ ⚠ same residue
CDKN1B p.Ser12Arg Uncertain significance ★ ⚠ same residue
CDKN1B p.Ser12Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1B p.Arg154Ter Pathogenic ★★ same condition
CDKN1B p.Arg5Ter Pathogenic/Likely pathogenic ★★ same condition
CDKN1B p.Gln104Ter 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-ser12 (accessed [today's date]).

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