Is CCND2 p.Ser271Leu (c.812C>T) pathogenic?

CCND2 p.Ser271Leu (c.812C>T) is classified Conflicting classifications of pathogenicity in CCND2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-16). AlphaMissense: likely benign (0.0799); Ultra-rare (popmax 0.0164%, mid).

How common is CCND2 p.Ser271Leu (c.812C>T) in the general population?

CCND2 p.Ser271Leu (c.812C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CCND2 p.Ser271Leu (c.812C>T)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

CCND2 p.Ser271Leu

c.812C>T · rs776036883 · VCV1483926

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.84	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 1.8	GERP 0.92, phastCons 0.91
Regional constraint	o/e 1.12	unconstrained · MANE · 108 bp · p 0.37 · regional, not allelic
Overall
CADD	16.42	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00167% 27/1,613,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.00169%	59,001
Finnishnot grpmax-eligible	0.00156%	64,016
South Asian	0.0011%	91,082

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.Ser271Leu
Coding: c.812C>T
MANE Select: NM_001759
dbSNP: rs776036883
Type: single nucleotide variant
Location: chr12:4299951 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.98 · 1 PDB
Residue 271: the 'disordered' region; a modified residue (phosphoserine)

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

Similar variants

CCND2 p.Ser271Ter Likely pathogenic ★★ 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.Thr280Ala Pathogenic ★★ same type
CCND2 p.Thr280Asn Pathogenic/Likely pathogenic ★★ same type
CCND2 p.Thr280Ile Pathogenic/Likely pathogenic ★★ same type
CCND2 p.Thr280Pro Pathogenic/Likely 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-ser271leu (accessed [today's date]).

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