CRB2 p.Arg704=
c.2112G>A · rs114090190 · VCV714443
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.862%, afr)
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 3.5 | GERP 0.82, phastCons 1 |
| Overall | ||
| CADD | 4.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.862%
African / African-American · 647/75,066 alleles
Filtering AF
0.807%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.785%
Overall
0.0436%
704/1,613,986 alleles · rare
exomes 340/1,461,640 · genomes 364/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.862% | 116 |
| Remaining individualsnot grpmax-eligible | 0.0592% | 1,689 |
| Admixed American | 0.0283% | 3,531 |
| European (non-Finnish) | 0.000254% | 393,345 |
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
- CRB2
- Protein
- p.Arg704=
- Coding
- c.2112G>A
- MANE Select
- NM_173689
- dbSNP
- rs114090190
- Type
- single nucleotide variant
- Location
- chr9:123371254 (GRCh38)
- Gene constraint
- LOEUF 1.202 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.95 · 1 PDB
- Residue 704
- the laminin g-like 2 domain; a UniProt-annotated variant site (in fsgs9; uncertain significance)
Similar variants
- CRB2 p.Arg704Trp Uncertain significance ★ ⚠ same residue
- CRB2 p.Arg704Gln Likely benign ★ same residue
- CRB2 p.Arg275Ter Pathogenic ★★ same type
- CRB2 p.Cys105Ter Pathogenic/Likely pathogenic ★★ same type
- CRB2 p.Gly1205Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
- CRB2 p.Trp759Ter Pathogenic ★★ same type
- CRB2 p.Ala1042Thr Uncertain significance ★★ ⚠ same type
- CRB2 p.Ala1266Pro Uncertain significance ★★ ⚠ same type
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/crb2-p-arg704 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown