Is CR2 p.His955fs (c.2864_2865del) pathogenic?

CR2 p.His955fs (c.28642865del) is classified Pathogenic in CR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). Very rare (popmax 0.000509%, nfe); Associated with immunodeficiency, common variable, 7.

What condition is associated with CR2 p.His955fs (c.2864_2865del)?

CR2 p.His955fs (c.2864_2865del) is associated with immunodeficiency, common variable, 7 (ClinVar).

How common is CR2 p.His955fs (c.2864_2865del) in the general population?

CR2 p.His955fs (c.2864_2865del) is very rare (popmax 0.000509%, nfe) (gnomAD).

CR2 p.His955fs

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.2864_2865del · rs2102308703 · VCV1469632

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000509%, 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 15 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1	GERP -3.1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,908 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,922 alleles · very rare exomes 6/1,461,596 · genomes 0/152,326 · 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.His955fs
Coding: c.2864_2865del
MANE Select: NM_001006658
dbSNP: rs2102308703
Type: Deletion
Location: chr1:207476381 (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.His955Tyr Uncertain significance ★ ⚠ same residue
CR2 p.Pro208fs Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Ser199fs Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Val1082fs Uncertain significance ★★ same condition
CR2 c.2155+7del Likely benign ★★ same condition
CR2 c.2156-20_2156-18del Likely benign ★★ same condition
CR2 c.3089-3del Benign/Likely benign ★★ same condition
CR2 c.3189-8_3189-7del Benign/Likely benign ★★ 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-his955fs (accessed [today's date]).

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