Is CDKN2D p.Gln152Pro (c.455A>C) pathogenic?

CDKN2D p.Gln152Pro (c.455A>C) is classified Uncertain significance in CDKN2D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1091); Absent from gnomAD v4.1.

How common is CDKN2D p.Gln152Pro (c.455A>C) in the general population?

CDKN2D p.Gln152Pro (c.455A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN2D p.Gln152Pro (c.455A>C)?

AlphaMissense predicts likely benign (score 0.1091) — an in-silico prediction, not a clinical call.

CDKN2D p.Gln152Pro

c.455A>C · VCV4651641

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1091 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,674)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1091	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -10.96	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 1.1, phastCons 0.96
Regional constraint	o/e 0.85	unconstrained · MANE · 1,592 bp · p 0.022 · regional, not allelic
Overall
CADD	13.02	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

No allele count reported in gnomAD v4.1 (AN 1,613,674). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDKN2D
Protein: p.Gln152Pro
Coding: c.455A>C
MANE Select: NM_001800
Type: single nucleotide variant
Location: chr19:10567104 (GRCh38)
Gene constraint: LOEUF 1.426 · pLI 0.24 (gnomAD)
Structure: AlphaFold pLDDT 95.91 · 2 PDB
Residue 152: an α-helix

Full CDKN2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN2D p.Ala128Pro Uncertain significance ★ ⚠ same type
CDKN2D p.Ala137Pro Uncertain significance ★ ⚠ same type
CDKN2D p.Ala146Thr Uncertain significance ★ ⚠ same type
CDKN2D p.Ala57Thr Uncertain significance ★ ⚠ same type
CDKN2D p.Arg7Pro Uncertain significance ★ ⚠ same type
CDKN2D p.Arg83Cys Uncertain significance ★ same type
CDKN2D p.Asp20Asn Uncertain significance ★ ⚠ same type
CDKN2D p.Glu23Gln Uncertain significance ★ ⚠ same type

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/cdkn2d-p-gln152pro (accessed [today's date]).

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