Is CCND2 p.Gln249His (c.747G>T) pathogenic?

CCND2 p.Gln249His (c.747G>T) is classified Uncertain significance in CCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely pathogenic (0.8408); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with CCND2 p.Gln249His (c.747G>T)?

CCND2 p.Gln249His (c.747G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CCND2 p.Gln249His (c.747G>T) in the general population?

CCND2 p.Gln249His (c.747G>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CCND2 p.Gln249His (c.747G>T)?

AlphaMissense predicts likely pathogenic (score 0.8408) — an in-silico prediction, not a clinical call.

CCND2 p.Gln249His

c.747G>T · rs149961693 · VCV2372854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8408 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8408	likely pathogenic
REVEL	0.322	indeterminate
SaProt	LLR -10.08	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 26 kb · p 7.7e-16 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00137% 20/1,461,804 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.00153%	65,555
African / African-American	0.00133%	75,036

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.Gln249His
Coding: c.747G>T
MANE Select: NM_001759
dbSNP: rs149961693
Type: single nucleotide variant
Location: chr12:4299886 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.98 · 1 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCND2 p.Pro281Ala Pathogenic ★★ same condition
CCND2 p.Arg178Cys Uncertain significance ★★ ⚠ same condition
CCND2 p.Ser222Leu Uncertain significance ★★ ⚠ same condition
CCND2 p.Gln215Ter Pathogenic ★ same condition
CCND2 p.Glu272Ter Pathogenic ★ same condition
CCND2 p.Ala120Ser Uncertain significance ★ ⚠ same condition
CCND2 p.Ala189Val Uncertain significance ★ ⚠ same condition
CCND2 p.Ala195Gly Uncertain significance ★ 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/ccnd2-p-gln249his (accessed [today's date]).

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