Is CR2 p.Ala348= (c.1044G>A) pathogenic?

CR2 p.Ala348= (c.1044G>A) is classified Likely benign in CR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). Ultra-rare (popmax 0.0133%, amr); Associated with immunodeficiency, common variable, 7.

What condition is associated with CR2 p.Ala348= (c.1044G>A)?

CR2 p.Ala348= (c.1044G>A) is associated with immunodeficiency, common variable, 7 (ClinVar).

How common is CR2 p.Ala348= (c.1044G>A) in the general population?

CR2 p.Ala348= (c.1044G>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

CR2 p.Ala348=

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.1044G>A · rs144982406 · VCV656901

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

immunodeficiency, common variable, 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.57	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -3.8	GERP -4
Overall
CADD	14.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,942 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.00254% 41/1,613,790 alleles · ultra-rare exomes 38/1,461,708 · genomes 3/152,082 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,493
East Asian	0.00891%	11,221
African / African-American	0.00401%	24,957
European (non-Finnish)	0.00212%	47,197
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Ala348=
Coding: c.1044G>A
MANE Select: NM_001006658
dbSNP: rs144982406
Type: single nucleotide variant
Location: chr1:207469921 (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 c.1225+1G>C Pathogenic ★★ same condition
CR2 c.3089-1G>A Likely pathogenic ★★ same condition
CR2 p.Arg142Ter Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Arg368Ter Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Arg392Ter Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Arg840Ter Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Cys154Ter Pathogenic ★★ same condition
CR2 p.Ala174Pro 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/cr2-p-ala348 (accessed [today's date]).

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