LRRC56 p.Pro466=
c.1398G>A · rs746149171 · VCV2185212
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -2.8 | GERP -1.7 |
| Overall | ||
| CADD | 1.414 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,074 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00136%
22/1,611,726 alleles · ultra-rare
exomes 20/1,459,622 · genomes 2/152,104 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,074 |
| African / African-American | 0.00534% | 18,715 |
| South Asian | 0.00439% | 22,769 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,428 |
| European (non-Finnish) | 0.00102% | 98,310 |
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
- LRRC56
- Protein
- p.Pro466=
- Coding
- c.1398G>A
- MANE Select
- NM_198075
- dbSNP
- rs746149171
- Type
- single nucleotide variant
- Location
- chr11:554045 (GRCh38)
- Gene constraint
- LOEUF 1.225 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 56.07
- Residue 466
- a UniProt-annotated variant site (in cild39); the 'disordered' region
Similar variants
- LRRC56 p.Pro466Leu Uncertain significance ★★ ⚠ same residue
- LRRC56 p.Pro466Arg Uncertain significance ★ ⚠ same residue
- HRAS c.291-6T>G Benign ★★★ same type
- HRAS p.Gly12= Likely benign ★★★ same type
- LRRC56 p.Tyr53Ter Pathogenic/Likely pathogenic ★★ same type
- HRAS p.Arg68Gly Uncertain significance ★★ ⚠ same type
- HRAS p.Lys88Arg Uncertain significance ★★ ⚠ same type
- HRAS p.Met111Leu 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/lrrc56-p-pro466 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown