Is CR2 p.Thr720= (c.2160A>G) pathogenic?

CR2 p.Thr720= (c.2160A>G) is classified Likely benign in CR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-21). Very rare (popmax 0.00439%, sas); Associated with immunodeficiency, common variable, 7.

What condition is associated with CR2 p.Thr720= (c.2160A>G)?

CR2 p.Thr720= (c.2160A>G) is associated with immunodeficiency, common variable, 7 (ClinVar).

How common is CR2 p.Thr720= (c.2160A>G) in the general population?

CR2 p.Thr720= (c.2160A>G) is very rare (popmax 0.00439%, sas) (gnomAD).

CR2 p.Thr720=

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.2160A>G · rs1489879720 · VCV1162113

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

immunodeficiency, common variable, 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP -3.4, phastCons 0.001
Overall
CADD	1.669	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,086 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000558% 9/1,614,038 alleles · very rare exomes 9/1,461,680 · genomes 0/152,358 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,772
European (non-Finnish)	0.000424%	235,980

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.Thr720=
Coding: c.2160A>G
MANE Select: NM_001006658
dbSNP: rs1489879720
Type: single nucleotide variant
Location: chr1:207473805 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.18 · 9 PDB
Residue 720: the sushi 12 domain

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-thr720 (accessed [today's date]).

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