Is CCND3 p.Pro17Ser (c.49C>T) pathogenic?

CCND3 p.Pro17Ser (c.49C>T) is classified Uncertain significance in CCND3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1258); Very rare (popmax 0.0012%, sas).

How common is CCND3 p.Pro17Ser (c.49C>T) in the general population?

CCND3 p.Pro17Ser (c.49C>T) is very rare (popmax 0.0012%, sas) (gnomAD).

What do computational predictors say about CCND3 p.Pro17Ser (c.49C>T)?

AlphaMissense predicts likely benign (score 0.1258) — an in-silico prediction, not a clinical call.

CCND3 p.Pro17Ser

c.49C>T · VCV4650039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1258 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0012%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1258	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -10.15	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 5.6	GERP 0.99, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 5,706 bp · p 0.00031 · regional, not allelic
Overall
CADD	19.02	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

Grpmax group 0.0012% South Asian · 1/83,548 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000289% 4/1,381,718 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0012%	83,548
European (non-Finnish)	0.000264%	379,458

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: CCND3
Protein: p.Pro17Ser
Coding: c.49C>T
MANE Select: NM_001760
Type: single nucleotide variant
Location: chr6:41941601 (GRCh38)
Gene constraint: LOEUF 0.548 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 87.70 · 2 PDB

Full CCND3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCND3 p.Ala131Thr Uncertain significance ★ ⚠ same type
CCND3 p.Ala154Ser Uncertain significance ★ ⚠ same type
CCND3 p.Ala204Thr Uncertain significance ★ ⚠ same type
CCND3 p.Ala230Val Uncertain significance ★ ⚠ same type
CCND3 p.Ala249Thr Uncertain significance ★ ⚠ same type
CCND3 p.Ala258Val Uncertain significance ★ ⚠ same type
CCND3 p.Ala269Thr Uncertain significance ★ ⚠ same type
CCND3 p.Arg10Pro 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/ccnd3-p-pro17ser (accessed [today's date]).

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