Is CR2 p.Pro1034Ser (c.3100C>T) pathogenic?

CR2 p.Pro1034Ser (c.3100C>T) is classified Uncertain significance in CR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-24). AlphaMissense: likely benign (0.1282); Very rare (popmax 8.57e-05%, nfe); Associated with immunodeficiency, common variable, 7.

What condition is associated with CR2 p.Pro1034Ser (c.3100C>T)?

CR2 p.Pro1034Ser (c.3100C>T) is associated with immunodeficiency, common variable, 7 (ClinVar).

How common is CR2 p.Pro1034Ser (c.3100C>T) in the general population?

CR2 p.Pro1034Ser (c.3100C>T) is very rare (popmax 8.57e-05%, nfe) (gnomAD).

What do computational predictors say about CR2 p.Pro1034Ser (c.3100C>T)?

AlphaMissense predicts likely benign (score 0.1282) — an in-silico prediction, not a clinical call.

CR2 p.Pro1034Ser

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.3100C>T · rs1558196448 · VCV1488101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1282 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.57e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency, common variable, 7

Computational evidence

Protein change
AlphaMissense	0.1282	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -7.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.56, phastCons 0.56
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.0053 · regional, not allelic
Overall
CADD	17.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P975S vs ClinVar P1034S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.57e-05% European (non-Finnish) · 1/1,166,616 alleles

Overall 6.26e-05% 1/1,598,710 alleles · very rare exomes 1/1,446,464 · genomes 0/152,246 · 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.Pro1034Ser
Coding: c.3100C>T
MANE Select: NM_001006658
dbSNP: rs1558196448
Type: single nucleotide variant
Location: chr1:207479268 (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.Pro1034= Likely benign ★★ same residue
CR2 p.Pro1034Ala Uncertain significance ★ ⚠ same residue
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

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-pro1034ser (accessed [today's date]).

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