Is CDKN1B p.Val109= (c.327C>T) pathogenic?

CDKN1B p.Val109= (c.327C>T) is classified Likely benign in CDKN1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-14). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Val109= (c.327C>T)?

CDKN1B p.Val109= (c.327C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN1B p.Val109= (c.327C>T) in the general population?

CDKN1B p.Val109= (c.327C>T) is absent from gnomAD v4.1 (gnomAD).

CDKN1B p.Val109=

c.327C>T · VCV3489637

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.76	GERP 1.5, phastCons 0.018
Overall
CADD	11.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKN1B
Protein: p.Val109=
Coding: c.327C>T
MANE Select: NM_004064
Type: single nucleotide variant
Location: chr12:12718166 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 109: a UniProt-annotated variant site (in); 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

Similar variants

CDKN1B p.Val109Ile Uncertain significance ★★ ⚠ same residue
CDKN1B p.Val109Gly Benign ★★ same residue
CDKN1B p.Val109Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1B p.Val109Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1B p.Val109fs Pathogenic ★★ same residue
CDKN1B p.Val109Ser Uncertain significance ★★ 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-val109 (accessed [today's date]).

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