Is CCND3 p.Arg271Leu (c.812G>T) pathogenic?

CCND3 p.Arg271Leu (c.812G>T) is classified Uncertain significance in CCND3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.1124); Very rare (popmax 8.48e-05%, nfe).

How common is CCND3 p.Arg271Leu (c.812G>T) in the general population?

CCND3 p.Arg271Leu (c.812G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CCND3 p.Arg271Leu (c.812G>T)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

CCND3 p.Arg271Leu

c.812G>T · VCV4222065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.33	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 5.8	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 5,706 bp · p 0.00031 · regional, not allelic
Overall
CADD	20.5	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 8.48e-05% European (non-Finnish) · 1/1,179,500 alleles

Overall 6.85e-05% 1/1,460,866 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: CCND3
Protein: p.Arg271Leu
Coding: c.812G>T
MANE Select: NM_001760
Type: single nucleotide variant
Location: chr6:41936007 (GRCh38)
Gene constraint: LOEUF 0.548 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 87.70 · 2 PDB
Residue 271: the 'disordered' region

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

Similar variants

CCND3 p.Arg271Gln Uncertain significance ★ ⚠ same residue
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

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-arg271leu (accessed [today's date]).

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