LRRC56 p.Pro452=
c.1356T>G · rs138194233 · VCV1631532
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.18%, amr)
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 -1.5 | GERP -2.3 |
| Overall | ||
| CADD | 1.041 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.18%
Admixed American · 707/59,968 alleles
Filtering AF
1.11%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.08%
Overall
0.791%
12,757/1,612,090 alleles · low-frequency
exomes 11,449/1,459,990 · genomes 1,308/152,100 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 1.18% | 85 |
| African / African-American | 0.938% | 107 |
| European (non-Finnish) | 0.876% | 114 |
| Remaining individualsnot grpmax-eligible | 0.769% | 130 |
| Finnishnot grpmax-eligible | 0.639% | 156 |
| Ashkenazi Jewishnot grpmax-eligible | 0.43% | 233 |
| Middle Eastern | 0.0661% | 1,514 |
| East Asian | 0.00669% | 14,952 |
| South Asian | 0.00439% | 22,770 |
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.Pro452=
- Coding
- c.1356T>G
- MANE Select
- NM_198075
- dbSNP
- rs138194233
- Type
- single nucleotide variant
- Location
- chr11:554003 (GRCh38)
- Gene constraint
- LOEUF 1.225 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 56.07
- Residue 452
- a UniProt-annotated variant site (in cild39); the 'disordered' region
Similar variants
- 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
- HRAS p.Pro174Ala Uncertain significance ★★ ⚠ same type
- HRAS p.Pro179Leu 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-pro452 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown