Is CDKN1B p.Ala149= (c.447A>T) pathogenic?

CDKN1B p.Ala149= (c.447A>T) is classified Likely benign in CDKN1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). Very rare (popmax 0.00269%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Ala149= (c.447A>T)?

CDKN1B p.Ala149= (c.447A>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN1B p.Ala149= (c.447A>T) in the general population?

CDKN1B p.Ala149= (c.447A>T) is very rare (popmax 0.00269%, afr) (gnomAD).

CDKN1B p.Ala149=

c.447A>T · rs2497405841 · VCV1740877

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

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 -3.3	GERP -3
Overall
CADD	3.598	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,216 alleles

Filtering AF 0.00125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.00165% 26/1,575,208 alleles · very rare exomes 26/1,423,216 · genomes 0/151,992 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,108
European (non-Finnish)	0.0019%	52,511
Remaining individualsnot grpmax-eligible	0.00163%	61,168
South Asian	0.00111%	90,454

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.Ala149=
Coding: c.447A>T
MANE Select: NM_004064
dbSNP: rs2497405841
Type: single nucleotide variant
Location: chr12:12718286 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 149: 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

Similar variants

CDKN1B p.Ala149Ser Uncertain significance ★★ ⚠ same residue
CDKN1B p.Ala149Pro Uncertain significance ★ ⚠ same residue
CDKN1B p.Ala149Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1B p.Ala149Val Uncertain significance ★ ⚠ same residue
CDKN1B p.Ala149fs Uncertain significance ★★ 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-ala149 (accessed [today's date]).

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