Is CR2 p.Val697Ala (c.2090T>C) pathogenic?

CR2 p.Val697Ala (c.2090T>C) is classified Uncertain significance in CR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-06). Absent from gnomAD v4.1; Associated with immunodeficiency, common variable, 7.

What condition is associated with CR2 p.Val697Ala (c.2090T>C)?

CR2 p.Val697Ala (c.2090T>C) is associated with immunodeficiency, common variable, 7 (ClinVar).

How common is CR2 p.Val697Ala (c.2090T>C) in the general population?

CR2 p.Val697Ala (c.2090T>C) is absent from gnomAD v4.1 (gnomAD).

CR2 p.Val697Ala

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.2090T>C · rs2527224079 · VCV1715336

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

immunodeficiency, common variable, 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.207	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -2.8, phastCons 0.97
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.0053 · regional, not allelic
Overall
CADD	18.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CR2
Protein: p.Val697Ala
Coding: c.2090T>C
MANE Select: NM_001006658
dbSNP: rs2527224079
Type: single nucleotide variant
Location: chr1:207473656 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.18 · 9 PDB
Residue 697: the sushi 11 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-val697ala (accessed [today's date]).

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