Is CR2 p.Phe383= (c.1149C>T) pathogenic?

CR2 p.Phe383= (c.1149C>T) is classified Likely benign in CR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-06). Ultra-rare (popmax 0.0494%, mid); Associated with immunodeficiency, common variable, 7.

What condition is associated with CR2 p.Phe383= (c.1149C>T)?

CR2 p.Phe383= (c.1149C>T) is associated with immunodeficiency, common variable, 7 (ClinVar).

How common is CR2 p.Phe383= (c.1149C>T) in the general population?

CR2 p.Phe383= (c.1149C>T) is ultra-rare (popmax 0.0494%, mid) (gnomAD).

CR2 p.Phe383=

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.1149C>T · rs756529992 · VCV1621588

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, mid)

Conditions

immunodeficiency, common variable, 7

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.23	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP 0.53	GERP 1.8, phastCons 0.99
Overall
CADD	16.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0494% Middle Eastern · 3/6,076 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00716%

Overall 0.000682% 11/1,613,872 alleles · ultra-rare exomes 10/1,461,680 · genomes 1/152,192 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0494%	2,025
African / African-American	0.00267%	37,452
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000424%	235,985

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.Phe383=
Coding: c.1149C>T
MANE Select: NM_001006658
dbSNP: rs756529992
Type: single nucleotide variant
Location: chr1:207470026 (GRCh38)

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

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-phe383 (accessed [today's date]).

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