Is CDKN2D p.Arg7Pro (c.20G>C) pathogenic?

CDKN2D p.Arg7Pro (c.20G>C) is classified Uncertain significance in CDKN2D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely benign (0.2168); Very rare (popmax 0.00204%, amr).

How common is CDKN2D p.Arg7Pro (c.20G>C) in the general population?

CDKN2D p.Arg7Pro (c.20G>C) is very rare (popmax 0.00204%, amr) (gnomAD).

What do computational predictors say about CDKN2D p.Arg7Pro (c.20G>C)?

AlphaMissense predicts likely benign (score 0.2168) — an in-silico prediction, not a clinical call.

CDKN2D p.Arg7Pro

c.20G>C · VCV3999804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2168 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00204%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2168	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -13.25	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 0.059	GERP -1.4, phastCons 0.42
Regional constraint	o/e 0.85	unconstrained · MANE · 1,592 bp · p 0.022 · regional, not allelic
Overall
CADD	15.43	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 0.00204% Admixed American · 1/48,962 alleles

Overall 7.38e-05% 1/1,354,532 alleles · very rare

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: CDKN2D
Protein: p.Arg7Pro
Coding: c.20G>C
MANE Select: NM_001800
Type: single nucleotide variant
Location: chr19:10568634 (GRCh38)
Gene constraint: LOEUF 1.426 · pLI 0.24 (gnomAD)
Structure: AlphaFold pLDDT 95.91 · 2 PDB

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.Arg83Cys Uncertain significance ★ same type
CDKN2D p.Asp20Asn Uncertain significance ★ ⚠ same type
CDKN2D p.Gln152Pro 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-arg7pro (accessed [today's date]).

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