LRRC56 p.Pro418=
c.1254T>C · rs567787669 · VCV2979830
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0791%, sas)
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 -0.19 | GERP -0.77, phastCons 0.001 |
| Overall | ||
| CADD | 4.834 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0791%
South Asian · 72/90,978 alleles
Filtering AF
0.0644%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.059%
Overall
0.00459%
74/1,611,276 alleles · ultra-rare
exomes 72/1,459,126 · genomes 2/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0791% | 1,264 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,382 |
| European (non-Finnish) | 8.48e-05% | 1,179,122 |
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.Pro418=
- Coding
- c.1254T>C
- MANE Select
- NM_198075
- dbSNP
- rs567787669
- Type
- single nucleotide variant
- Location
- chr11:552641 (GRCh38)
- Gene constraint
- LOEUF 1.225 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 56.07
- Residue 418
- 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-pro418 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown