Is CCND2 p.Thr115Ser (c.344C>G) pathogenic?

CCND2 p.Thr115Ser (c.344C>G) is classified Uncertain significance in CCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: ambiguous (0.3602); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with CCND2 p.Thr115Ser (c.344C>G)?

CCND2 p.Thr115Ser (c.344C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CCND2 p.Thr115Ser (c.344C>G) in the general population?

CCND2 p.Thr115Ser (c.344C>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CCND2 p.Thr115Ser (c.344C>G)?

AlphaMissense predicts ambiguous (score 0.3602) — an in-silico prediction, not a clinical call.

CCND2 p.Thr115Ser

c.344C>G · rs762132499 · VCV3139899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3602	ambiguous
REVEL	0.223	benign-leaning
SaProt	LLR -8.86	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 26 kb · p 7.7e-16 · regional, not allelic
Overall
CADD	22.7	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 0.00446% East Asian · 2/44,890 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000137% 2/1,461,884 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: CCND2
Protein: p.Thr115Ser
Coding: c.344C>G
MANE Select: NM_001759
dbSNP: rs762132499
Type: single nucleotide variant
Location: chr12:4276153 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.98 · 1 PDB
Residue 115: the cyclin n-terminal domain

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.Thr115Pro Uncertain significance ★ ⚠ same residue
CCND2 p.Thr115Ile Uncertain significance ★ ⚠ same residue
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

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-thr115ser (accessed [today's date]).

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