Is CCND2 p.Arg262His (c.785G>A) pathogenic?

CCND2 p.Arg262His (c.785G>A) is classified Benign/Likely benign in CCND2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-18). AlphaMissense: likely benign (0.0779); Ultra-rare (popmax 0.0587%, afr).

How common is CCND2 p.Arg262His (c.785G>A) in the general population?

CCND2 p.Arg262His (c.785G>A) is ultra-rare (popmax 0.0587%, afr) (gnomAD).

What do computational predictors say about CCND2 p.Arg262His (c.785G>A)?

AlphaMissense predicts likely benign (score 0.0779) — an in-silico prediction, not a clinical call.

CCND2 p.Arg262His

c.785G>A · rs142170178 · VCV376994

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0779 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0587%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0779	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -6.71	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 6.4	GERP -0.19, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 108 bp · p 0.37 · 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 0.0587% African / African-American · 44/75,020 alleles

Filtering AF 0.0448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.04%

Overall 0.068% 1,097/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.704%	142
Remaining individualsnot grpmax-eligible	0.0848%	1,179
African / African-Americangrpmax	0.0587%	1,705
Admixed American	0.045%	2,223
European (non-Finnish)	0.0433%	2,309
South Asian	0.00878%	11,385
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
East Asian	0.00223%	44,882

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg262His
Coding: c.785G>A
MANE Select: NM_001759
dbSNP: rs142170178
Type: single nucleotide variant
Location: chr12:4299924 (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

Similar variants

CCND2 p.Arg262Cys Uncertain significance ★ ⚠ 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.Ser271Ter 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

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-arg262his (accessed [today's date]).

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