Is CCND2 p.Arg285Gln (c.854G>A) pathogenic?

CCND2 p.Arg285Gln (c.854G>A) is classified Uncertain significance in CCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-01). AlphaMissense: likely benign (0.1538); Ultra-rare (popmax 0.0154%, sas).

How common is CCND2 p.Arg285Gln (c.854G>A) in the general population?

CCND2 p.Arg285Gln (c.854G>A) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

What do computational predictors say about CCND2 p.Arg285Gln (c.854G>A)?

AlphaMissense predicts likely benign (score 0.1538) — an in-silico prediction, not a clinical call.

CCND2 p.Arg285Gln

c.854G>A · rs753881524 · VCV2642581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1538 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1538	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -5.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.84, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 108 bp · p 0.37 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% South Asian · 14/91,054 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.0044% 71/1,613,704 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,504
Remaining individualsnot grpmax-eligible	0.0048%	20,823
East Asian	0.00446%	22,440
European (non-Finnish)	0.00432%	23,135
Admixed American	0.00167%	59,964

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: CCND2
Protein: p.Arg285Gln
Coding: c.854G>A
MANE Select: NM_001759
dbSNP: rs753881524
Type: single nucleotide variant
Location: chr12:4299993 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.98 · 1 PDB
Residue 285: the 'disordered' region

Full CCND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCND2 p.Arg285Gly Uncertain significance ★ ⚠ same residue
CCND2 p.Arg285= Likely benign same residue
CCND2 p.Arg285_Asp286insValArg Uncertain significance ★ same residue
CCND2 p.Gln277Ter Pathogenic/Likely pathogenic ★★ same type
CCND2 p.Pro281Ala Pathogenic ★★ ⚠ same type
CCND2 p.Pro281Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
CCND2 p.Ser271Ter Likely pathogenic ★★ same type
CCND2 p.Thr280Ala Pathogenic ★★ ⚠ 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/ccnd2-p-arg285gln (accessed [today's date]).

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