Is CC2D2A c.1017+142del pathogenic?

CC2D2A c.1017+142del is classified Benign in CC2D2A (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-28). Common (popmax 31.9%, eas) — too common for a highly-penetrant pathogenic allele.

CC2D2A c.1017+142del

Q: How common is CC2D2A c.1017+142del in the general population?

CC2D2A c.1017+142del is common (popmax 31.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs58218122 · VCV1260314

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 31.9%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
Splice region	donor +142	deep intronic (+142 nt into the intron)
SpliceAI	—	not assessed · substitutions only
Overall
CADD	0.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.9% East Asian · 8,243/25,876 alleles

Filtering AF 31.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 31%

Overall 30.4% 215,802/709,822 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	35.7%	3
Ashkenazi Jewishnot grpmax-eligible	34.3%	3
Remaining individualsnot grpmax-eligible	32.9%	3
East Asiangrpmax	31.9%	3
European (non-Finnish)	30.4%	3
South Asian	27.8%	4
Admixed American	26.9%	4
African / African-American	26.6%	4
Middle Eastern	26.4%	4
Amishnot grpmax-eligible	24.7%	4

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: CC2D2A
Coding: c.1017+142del
MANE Select: NM_001378615
dbSNP: rs58218122
Type: Deletion
Location: chr4:15516134 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46

Full CC2D2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CC2D2A c.3289delG Pathogenic ★★ same type
CC2D2A c.3597_3600del Pathogenic/Likely pathogenic ★★ same type
CC2D2A c.4179+1del Pathogenic ★★ same type
CC2D2A p.Ala1197fs Pathogenic/Likely pathogenic ★★ same type
CC2D2A p.Ala447fs Pathogenic/Likely pathogenic ★★ same type
CC2D2A p.Asp1227fs Likely pathogenic ★★ same type
CC2D2A p.Asp1489fs Pathogenic/Likely pathogenic ★★ same type
CC2D2A p.Gln280fs 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/cc2d2a-c-1017-plus-142del (accessed [today's date]).

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