Is CDKN1B p.Ala55= (c.165G>A) pathogenic?

CDKN1B p.Ala55= (c.165G>A) is classified Benign in CDKN1B (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.04%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Ala55= (c.165G>A)?

CDKN1B p.Ala55= (c.165G>A) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Ala55= (c.165G>A) in the general population?

CDKN1B p.Ala55= (c.165G>A) is low-frequency (popmax 4.04%, eas) (gnomAD).

CDKN1B p.Ala55=

c.165G>A · rs16908375 · VCV239617

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.04%, eas)

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 -1.8	GERP -3.1
Overall
CADD	3.679	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.04% East Asian · 1,811/44,880 alleles

Filtering AF 3.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.82%

Overall 0.168% 2,709/1,614,226 alleles · low-frequency exomes 2,493/1,461,892 · genomes 216/152,334 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	4.04%	25
South Asian	0.815%	123
Remaining individualsnot grpmax-eligible	0.138%	727
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00551%	18,154
African / African-American	0.004%	25,021
Admixed American	0.00167%	60,028

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.Ala55=
Coding: c.165G>A
MANE Select: NM_004064
dbSNP: rs16908375
Type: single nucleotide variant
Location: chr12:12718004 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 55: the 'interaction with cdk2' 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 1 multiple endocrine neoplasia type 4

Similar variants

CDKN1B p.Ala55Glu Uncertain significance ★ ⚠ same residue
CDKN1B p.Ala55Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1B p.Ala55Val 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

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-ala55 (accessed [today's date]).

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