LRRC7 p.Arg417=
c.1251A>G · VCV3540217
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0169%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.85 | GERP -5.5, phastCons 0.96 |
| Overall | ||
| CADD | 8.276 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0169%
Middle Eastern · 1/5,928 alleles
Filtering AF
0.00466%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00343%
Overall
0.00323%
51/1,580,196 alleles · ultra-rare
exomes 49/1,427,992 · genomes 2/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0169% | 5,928 |
| Remaining individualsnot grpmax-eligible | 0.0148% | 6,752 |
| South Asian | 0.00947% | 10,559 |
| Admixed American | 0.00371% | 26,937 |
| European (non-Finnish) | 0.00266% | 37,610 |
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.Arg417=
- Coding
- c.1251A>G
- MANE Select
- NM_001370785
- Type
- single nucleotide variant
- Location
- chr1:70016465 (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 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
- LRRC7 c.1135-2A>G 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-arg417 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown