Is CC2D2B p.Arg1101Gln (c.3302G>A) pathogenic?

CC2D2B p.Arg1101Gln (c.3302G>A) is classified Uncertain significance in CC2D2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-04). AlphaMissense: ambiguous (0.3788); Ultra-rare (popmax 0.0267%, afr).

How common is CC2D2B p.Arg1101Gln (c.3302G>A) in the general population?

CC2D2B p.Arg1101Gln (c.3302G>A) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about CC2D2B p.Arg1101Gln (c.3302G>A)?

AlphaMissense predicts ambiguous (score 0.3788) — an in-silico prediction, not a clinical call.

CC2D2B p.Arg1101Gln

c.3302G>A · rs373755580 · VCV2514986

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3788	ambiguous
REVEL	0.877	moderately pathogenic-leaning
SaProt	LLR -9.65	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 41 kb · p 0.0003 · regional, not allelic
Overall
CADD	29.8	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 0.0267% African / African-American · 20/74,888 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00254% 41/1,612,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,744
Remaining individualsnot grpmax-eligible	0.00481%	20,811
Admixed American	0.00333%	29,989
East Asian	0.00223%	44,814
European (non-Finnish)	0.00119%	84,206
South Asian	0.0011%	91,052

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: CC2D2B
Protein: p.Arg1101Gln
Coding: c.3302G>A
MANE Select: NM_001349008
dbSNP: rs373755580
Type: single nucleotide variant
Location: chr10:96012605 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.49

Full CC2D2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CC2D2B p.Arg1329Gln Uncertain significance ★ ⚠ same type
CC2D2B p.Arg1345Pro Uncertain significance ★ ⚠ same type
CC2D2B p.Asn1422Ser Uncertain significance ★ ⚠ same type
CC2D2B p.Asp1248Asn Uncertain significance ★ ⚠ same type
CC2D2B p.Asp1312Glu Uncertain significance ★ ⚠ same type
CC2D2B p.Cys1234Arg Uncertain significance ★ ⚠ same type
CC2D2B p.Cys985Tyr Uncertain significance ★ ⚠ same type
CC2D2B p.Gln1128Glu 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/cc2d2b-p-arg1101gln (accessed [today's date]).

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