Is CDKN1B p.Cys148Phe (c.443G>T) pathogenic?

CDKN1B p.Cys148Phe (c.443G>T) is classified Conflicting classifications of pathogenicity in CDKN1B (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.1013); Ultra-rare (popmax 0.0579%, eas); Associated with ovarian cancer.

What condition is associated with CDKN1B p.Cys148Phe (c.443G>T)?

CDKN1B p.Cys148Phe (c.443G>T) is associated with ovarian cancer, multiple endocrine neoplasia type 4, hereditary neoplastic syndrome (ClinVar).

How common is CDKN1B p.Cys148Phe (c.443G>T) in the general population?

CDKN1B p.Cys148Phe (c.443G>T) is ultra-rare (popmax 0.0579%, eas) (gnomAD).

What do computational predictors say about CDKN1B p.Cys148Phe (c.443G>T)?

AlphaMissense predicts likely benign (score 0.1013) — an in-silico prediction, not a clinical call.

CDKN1B p.Cys148Phe

c.443G>T · rs200476090 · VCV571877

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1013 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0579%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.1013	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 1,103 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0579% East Asian · 26/44,886 alleles

Filtering AF 0.0405% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0347%

Overall 0.00168% 27/1,606,464 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0579%	1,726
South Asian	0.0011%	91,084

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.Cys148Phe
Coding: c.443G>T
MANE Select: NM_004064
dbSNP: rs200476090
Type: single nucleotide variant
Location: chr12:12718282 (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

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple endocrine neoplasia type 4 hereditary neoplastic syndrome

Similar variants

CDKN1B p.Cys148Arg Uncertain significance ★★ ⚠ same residue
CDKN1B p.Cys148Trp Uncertain significance ★★ ⚠ same residue
CDKN1B p.Cys148= Likely benign ★★ same residue
CDKN1B p.Cys148Ter Pathogenic ★ 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-cys148phe (accessed [today's date]).

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