Is C2CD3 c.1843+100del pathogenic?

C2CD3 c.1843+100del is classified Benign in C2CD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-10). Common (popmax 20.9%, eas) — too common for a highly-penetrant pathogenic allele.

C2CD3 c.1843+100del

Q: How common is C2CD3 c.1843+100del in the general population?

C2CD3 c.1843+100del is common (popmax 20.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs548567656 · VCV1296090

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 20.9%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +100	deep intronic (+100 nt into the intron)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.79	GERP -0.48
Overall
CADD	0.497	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.9% East Asian · 5,336/25,486 alleles

Filtering AF 20.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.3%

Overall 19.2% 89,599/467,162 alleles · common

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	21.3%	5
East Asiangrpmax	20.9%	5
European (non-Finnish)	19.5%	5
Ashkenazi Jewishnot grpmax-eligible	19.4%	5
Finnishnot grpmax-eligible	19.2%	5
South Asian	18.9%	5
Middle Eastern	18.9%	5
African / African-American	18.5%	5
Admixed American	14.8%	7

Remaining individuals 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: C2CD3
Coding: c.1843+100del
MANE Select: NM_001286577
dbSNP: rs548567656
Type: Deletion
Location: chr11:74113680 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65

Full C2CD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD3 c.708-2_708-1del Likely pathogenic ★★ same type
C2CD3 p.Ala913fs Pathogenic/Likely pathogenic ★★ same type
C2CD3 c.5496-6del Benign/Likely benign ★★ same type
C2CD3 c.5496-7_5496-6del Benign ★★ same type
C2CD3 c.1962+1del Pathogenic ★ same type
C2CD3 c.708-2del Likely pathogenic ★ same type
C2CD3 p.Arg844fs Pathogenic ★ same type
C2CD3 p.Cys1114fs 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/c2cd3-c-1843-plus-100del (accessed [today's date]).

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