LRRC7 p.Pro592Leu
c.1775C>T · rs781712945 · VCV2524229
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0236%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.084 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.7, phastCons 1 |
| Regional constraint | o/e 0.84 | unconstrained · MANE · 55 kb · p 2.5e-08 · regional, not allelic |
| Overall | ||
| CADD | 22.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0236%
Admixed American · 14/59,430 alleles
Filtering AF
0.0142%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0113%
Overall
0.000874%
14/1,602,126 alleles · ultra-rare
exomes 13/1,449,964 · genomes 1/152,162 · joint denominator
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
- LRRC7
- Protein
- p.Pro592Leu
- Coding
- c.1775C>T
- MANE Select
- NM_001370785
- dbSNP
- rs781712945
- Type
- single nucleotide variant
- Location
- chr1:70023355 (GRCh38)
- Gene constraint
- LOEUF 0.203 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 52.05 · 2 PDB
Similar variants
- LRRC7 p.Ala1105Thr Uncertain significance ★★ same type
- LRRC7 p.Ser354Ala Uncertain significance ★★ same type
- LRRC7 p.Arg417= Likely benign ★★ same type
- LRRC7 c.787-1G>T Pathogenic ★ same type
- LRRC7 p.Gln748Ter Pathogenic ★ same type
- LRRC7 p.Gly1049Ter Pathogenic ★ same type
- LRRC7 p.Leu122Arg Likely pathogenic ★ same type
- LRRC7 c.1005-7T>A 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/lrrc7-p-pro592leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown