Is CC2D1A p.Pro84= (c.252G>A) pathogenic?

CC2D1A p.Pro84= (c.252G>A) is classified Benign in CC2D1A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 30.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CC2D1A p.Pro84= (c.252G>A)?

CC2D1A p.Pro84= (c.252G>A) is associated with Inborn genetic diseases (ClinVar).

CC2D1A p.Pro84=

Q: How common is CC2D1A p.Pro84= (c.252G>A) in the general population?

CC2D1A p.Pro84= (c.252G>A) is common (popmax 30.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.252G>A · rs7250180 · VCV128620

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 30.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.6	GERP -3.5
Overall
CADD	1.451	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.4% African / African-American · 22,773/74,918 alleles

Filtering AF 30.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.9%

Overall 1.79% 28,877/1,613,230 alleles · common exomes 15,527/1,461,078 · genomes 13,350/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	30.4%	3
Remaining individualsnot grpmax-eligible	2.37%	42
Middle Eastern	2.29%	44
Admixed American	2.24%	45
South Asian	1%	100
Ashkenazi Jewishnot grpmax-eligible	0.551%	181
Amishnot grpmax-eligible	0.549%	182
European (non-Finnish)	0.174%	575
Finnishnot grpmax-eligible	0.00938%	10,658
East Asian	0.00892%	11,212

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: CC2D1A
Protein: p.Pro84=
Coding: c.252G>A
MANE Select: NM_017721
dbSNP: rs7250180
Type: single nucleotide variant
Location: chr19:13912378 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB
Residue 84: the 'disordered' region

Full CC2D1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CC2D1A p.Pro84Leu Likely benign ★ same residue
CC2D1A p.Pro84Ser Uncertain significance ★ ⚠ same residue
CC2D1A c.61-2A>G Likely pathogenic ★★ same condition
CC2D1A c.1941-6C>T Uncertain significance ★★ same condition
CC2D1A c.2073+5G>T Uncertain significance ★★ same condition
CC2D1A c.946+6A>G Uncertain significance ★★ same condition
CC2D1A p.Ala154Thr Uncertain significance ★★ ⚠ same condition
CC2D1A p.Ala481Val Uncertain significance ★★ ⚠ same condition

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/cc2d1a-p-pro84 (accessed [today's date]).

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