Is CDKN1B p.Lys25= (c.75G>A) pathogenic?

CDKN1B p.Lys25= (c.75G>A) is classified Likely benign in CDKN1B (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0166%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Lys25= (c.75G>A)?

CDKN1B p.Lys25= (c.75G>A) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Lys25= (c.75G>A) in the general population?

CDKN1B p.Lys25= (c.75G>A) is ultra-rare (popmax 0.0166%, nfe) (gnomAD).

CDKN1B p.Lys25=

c.75G>A · rs367611328 · VCV412891

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, nfe)

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 1	GERP -0.61, phastCons 1
Overall
CADD	8.641	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% European (non-Finnish) · 196/1,180,060 alleles

Filtering AF 0.0147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.0138% 222/1,614,088 alleles · ultra-rare exomes 208/1,461,826 · genomes 14/152,262 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0176%	5,681
European (non-Finnish)grpmax	0.0166%	6,021
Admixed American	0.015%	6,668
South Asian	0.00329%	30,364
African / African-American	0.00267%	37,474
Finnishnot grpmax-eligible	0.00156%	63,988

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys25=
Coding: c.75G>A
MANE Select: NM_004064
dbSNP: rs367611328
Type: single nucleotide variant
Location: chr12:12717914 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 25: 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.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
CDKN1B p.Gln20Ter Pathogenic ★★ same condition
CDKN1B p.Gln57Ter Pathogenic/Likely 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-lys25 (accessed [today's date]).

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