Is CDKN1B p.His129= (c.387T>C) pathogenic?

CDKN1B p.His129= (c.387T>C) is classified Likely benign in CDKN1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Very rare (popmax 0.00924%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.His129= (c.387T>C)?

CDKN1B p.His129= (c.387T>C) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.His129= (c.387T>C) in the general population?

CDKN1B p.His129= (c.387T>C) is very rare (popmax 0.00924%, nfe) (gnomAD).

CDKN1B p.His129=

c.387T>C · rs377573215 · VCV485501

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00924%, 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 -0.31	GERP -2.6, phastCons 0.31
Overall
CADD	4.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00924% European (non-Finnish) · 109/1,180,010 alleles

Filtering AF 0.00782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.00701% 113/1,612,656 alleles · very rare exomes 102/1,460,454 · genomes 11/152,202 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00924%	10,826
African / African-American	0.004%	24,979
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.His129=
Coding: c.387T>C
MANE Select: NM_004064
dbSNP: rs377573215
Type: single nucleotide variant
Location: chr12:12718226 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 129: 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.His129Arg Uncertain significance ★★ ⚠ same residue
CDKN1B p.His129Tyr Uncertain significance ★★ ⚠ same residue
CDKN1B p.His129Asn Uncertain significance ★ ⚠ same residue
CDKN1B p.His129Gln Uncertain significance ★ ⚠ same residue
CDKN1B p.His129Leu Uncertain significance ★ ⚠ same residue
CDKN1B p.His129fs Pathogenic ★ same residue
CDKN1B p.Arg154Ter Pathogenic ★★ same condition
CDKN1B p.Arg5Ter 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-his129 (accessed [today's date]).

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