RHO p.Leu165=
c.495G>T · rs777283396 · VCV756243
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00833%, amr)
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 6.7 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 6.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00833%
Admixed American · 5/60,012 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00031%
5/1,614,084 alleles · very rare
exomes 4/1,461,820 · genomes 1/152,264 · 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
- RHO
- Protein
- p.Leu165=
- Coding
- c.495G>T
- MANE Select
- NM_000539
- dbSNP
- rs777283396
- Type
- single nucleotide variant
- Location
- chr3:129531009 (GRCh38)
- Gene constraint
- LOEUF 0.91 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.18 · 4 PDB
- Residue 165
- an α-helix
Similar variants
- RHO p.Leu165Pro Uncertain significance ★ ⚠ same residue
- RHO c.696+1G>C Likely pathogenic ★★ same type
- RHO c.936+1G>T Pathogenic/Likely pathogenic ★★ same type
- RHO c.937-1G>A Pathogenic ★★ same type
- RHO c.937-1G>T Pathogenic ★★ same type
- RHO c.937-2A>G Pathogenic/Likely pathogenic ★★ same type
- RHO c.937-2A>T Pathogenic/Likely pathogenic ★★ same type
- RHO p.Ala164Glu Pathogenic ★★ 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/rho-p-leu165 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown