Is CDKN1B p.Pro91= (c.273C>T) pathogenic?

CDKN1B p.Pro91= (c.273C>T) is classified Likely benign in CDKN1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0117%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Pro91= (c.273C>T)?

CDKN1B p.Pro91= (c.273C>T) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Pro91= (c.273C>T) in the general population?

CDKN1B p.Pro91= (c.273C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

CDKN1B p.Pro91=

c.273C>T · rs761928140 · VCV412884

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

hereditary neoplastic syndrome

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 0.6	GERP -2.9, phastCons 1
Overall
CADD	11.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,014 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00576% 93/1,614,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
European (non-Finnish)	0.00644%	15,527
African / African-American	0.00534%	18,736
South Asian	0.00439%	22,773
East Asian	0.00223%	44,900
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Pro91=
Coding: c.273C>T
MANE Select: NM_004064
dbSNP: rs761928140
Type: single nucleotide variant
Location: chr12:12718112 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 91: the 'interaction with cdk2' region; the 'disordered' region; an α-helix

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.Pro91Ala Uncertain significance ★★ ⚠ same residue
CDKN1B p.Pro91His Uncertain significance ★★ ⚠ same residue
CDKN1B p.Pro91Leu Uncertain significance ★★ ⚠ same residue
CDKN1B p.Pro91Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1B p.Pro91Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1B p.Pro91Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1B p.Pro91fs Pathogenic ★ same residue
CDKN1B p.Arg154Ter 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-pro91 (accessed [today's date]).

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