CRB2 p.Arg391=
c.1173C>T · VCV4807143
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8 | GERP -3.9 |
| Overall | ||
| CADD | 0.443 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
African / African-American · 37/75,064 alleles
Filtering AF
0.0368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0324%
Overall
0.00403%
65/1,613,208 alleles · ultra-rare
exomes 31/1,460,864 · genomes 34/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0493% | 2,029 |
| East Asian | 0.0134% | 7,480 |
| Admixed American | 0.00666% | 15,006 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,624 |
| South Asian | 0.00549% | 18,218 |
| Finnishnot grpmax-eligible | 0.00159% | 63,068 |
| European (non-Finnish) | 0.000678% | 147,501 |
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.Arg391=
- Coding
- c.1173C>T
- MANE Select
- NM_173689
- Type
- single nucleotide variant
- Location
- chr9:123370226 (GRCh38)
- Gene constraint
- LOEUF 1.202 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.95 · 1 PDB
- Residue 391
- the egf-like 8; calcium-binding domain; a UniProt-annotated variant site (in fsgs9; uncertain significance)
Similar variants
- CRB2 p.Arg391Cys Uncertain significance ★★ ⚠ 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
- CRB2 p.Ala228Thr 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-arg391 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown