Is CR2 p.Glu1007fs (c.3017dup) pathogenic?

CR2 p.Glu1007fs (c.3017dup) is classified Uncertain significance in CR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-23). Very rare (popmax 0.00136%, nfe); Associated with immunodeficiency, common variable, 7.

What condition is associated with CR2 p.Glu1007fs (c.3017dup)?

CR2 p.Glu1007fs (c.3017dup) is associated with immunodeficiency, common variable, 7 (ClinVar).

How common is CR2 p.Glu1007fs (c.3017dup) in the general population?

CR2 p.Glu1007fs (c.3017dup) is very rare (popmax 0.00136%, nfe) (gnomAD).

CR2 p.Glu1007fs

Q: How is Common variable immunodeficiency phenotype due to CD21 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.3017dup · rs779475083 · VCV845842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Conditions

immunodeficiency, common variable, 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.97, phastCons 0.98
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,179,962 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.000991% 16/1,613,846 alleles · very rare exomes 15/1,461,718 · genomes 1/152,128 · joint denominator

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: CR2
Protein: p.Glu1007fs
Coding: c.3017dup
MANE Select: NM_001006658
dbSNP: rs779475083
Type: Duplication
Location: chr1:207477998 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.18 · 9 PDB

Full CR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency, common variable, 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Common variable immunodeficiency phenotype due to CD21 deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

CR2 p.Leu198fs Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Leu819fs Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Thr209fs Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Gln726fs Pathogenic ★ same condition
CR2 p.Ile870fs Pathogenic ★ same condition
CR2 p.Val14fs Pathogenic ★ same condition
CR2 p.Gly337_Pro338insGly Uncertain significance ★ same condition
CR2 c.1225+1G>C Pathogenic ★★ 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/cr2-p-glu1007fs (accessed [today's date]).

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