Is CDKN1B p.Ala18= (c.54C>T) pathogenic?

CDKN1B p.Ala18= (c.54C>T) is classified Conflicting classifications of pathogenicity in CDKN1B (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.0217%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Ala18= (c.54C>T)?

CDKN1B p.Ala18= (c.54C>T) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Ala18= (c.54C>T) in the general population?

CDKN1B p.Ala18= (c.54C>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

CDKN1B p.Ala18=

c.54C>T · rs151027466 · VCV412885

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, 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 2.1	GERP 0.46, phastCons 0.98
Overall
CADD	14.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/60,018 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00211% 34/1,613,932 alleles · ultra-rare exomes 19/1,461,710 · genomes 15/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,617
Remaining individualsnot grpmax-eligible	0.0192%	5,207
Finnishnot grpmax-eligible	0.00156%	63,920
European (non-Finnish)	0.000678%	147,505

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.Ala18=
Coding: c.54C>T
MANE Select: NM_004064
dbSNP: rs151027466
Type: single nucleotide variant
Location: chr12:12717893 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 18: 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.Ala18Gly Uncertain significance ★★ ⚠ same residue
CDKN1B p.Ala18Val Uncertain significance ★★ ⚠ 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
CDKN1B p.Gln141Ter Pathogenic ★★ same condition
CDKN1B p.Gln163Ter 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-ala18 (accessed [today's date]).

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