Is CR2 p.Val375fs (c.1124_1125del) pathogenic?

CR2 p.Val375fs (c.11241125del) is classified Likely pathogenic in CR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-29). No gnomAD frequency available for this variant; Associated with CR2-related disorder.

What condition is associated with CR2 p.Val375fs (c.1124_1125del)?

CR2 p.Val375fs (c.1124_1125del) is associated with CR2-related disorder, systemic lupus erythematosus, susceptibility to, 9 (ClinVar).

How common is CR2 p.Val375fs (c.1124_1125del) in the general population?

CR2 p.Val375fs (c.1124_1125del) is no gnomAD frequency available for this variant (gnomAD).

CR2 p.Val375fs

c.1124_1125del · rs2527215447 · VCV3065971

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

CR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 1.8, phastCons 0.57

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CR2
Protein: p.Val375fs
Coding: c.1124_1125del
MANE Select: NM_001006658
dbSNP: rs2527215447
Type: Microsatellite
Location: chr1:207469999 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.18 · 9 PDB
Residue 375: the sushi 6 domain

Full CR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CR2-related disorder

Also linked: systemic lupus erythematosus, susceptibility to, 9

Similar variants

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.Pro208fs Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Arg1063Cys Uncertain significance ★★ ⚠ same condition
CR2 p.Asn492Ser Uncertain significance ★★ ⚠ same condition
CR2 p.Glu83Asp Uncertain significance ★★ ⚠ same condition
CR2 p.Gly563Arg 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-val375fs (accessed [today's date]).

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