Is CDKN1B p.Cys148= (c.444C>T) pathogenic?

CDKN1B p.Cys148= (c.444C>T) is classified Likely benign in CDKN1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-20). Very rare (popmax 0.00667%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Cys148= (c.444C>T)?

CDKN1B p.Cys148= (c.444C>T) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Cys148= (c.444C>T) in the general population?

CDKN1B p.Cys148= (c.444C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

CDKN1B p.Cys148=

c.444C>T · rs1302236491 · VCV1628997

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, 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 2.7	GERP 1.5, phastCons 0.99
Overall
CADD	13.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,988 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000374% 6/1,606,070 alleles · very rare exomes 2/1,453,892 · genomes 4/152,178 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,997
Remaining individualsnot grpmax-eligible	0.0016%	62,428
European (non-Finnish)	8.47e-05%	1,179,976

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.Cys148=
Coding: c.444C>T
MANE Select: NM_004064
dbSNP: rs1302236491
Type: single nucleotide variant
Location: chr12:12718283 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 148: 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.Cys148Arg Uncertain significance ★★ ⚠ same residue
CDKN1B p.Cys148Trp Uncertain significance ★★ ⚠ same residue
CDKN1B p.Cys148Ter Pathogenic ★ same residue
CDKN1B p.Cys148Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1B p.Cys148Tyr 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-cys148 (accessed [today's date]).

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