Is CC2D2B p.Arg380= (c.1140G>A) pathogenic?

CC2D2B p.Arg380= (c.1140G>A) is classified Likely benign in CC2D2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-01). Rare (popmax 0.617%, afr).

How common is CC2D2B p.Arg380= (c.1140G>A) in the general population?

CC2D2B p.Arg380= (c.1140G>A) is rare (popmax 0.617%, afr) (gnomAD).

CC2D2B p.Arg380=

c.1140G>A · rs41291590 · VCV2640722

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.617%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.34	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.92	GERP -1.3, phastCons 1
Overall
CADD	6.036	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.617% African / African-American · 398/64,466 alleles

Filtering AF 0.567% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.55%

Overall 0.549% 6,762/1,231,506 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.877%	114
Finnishnot grpmax-eligible	0.778%	129
African / African-Americangrpmax	0.617%	162
European (non-Finnish)	0.568%	176
Middle Eastern	0.563%	178
Remaining individualsnot grpmax-eligible	0.507%	197
South Asian	0.473%	211
Admixed American	0.325%	308
Ashkenazi Jewishnot grpmax-eligible	0.308%	324

Amish 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: CC2D2B
Protein: p.Arg380=
Coding: c.1140G>A
MANE Select: NM_001349008
dbSNP: rs41291590
Type: single nucleotide variant
Location: chr10:95961859 (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.Arg1101Gln Uncertain significance ★ ⚠ same type
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

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-arg380 (accessed [today's date]).

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