RPGRIP1L p.Pro883=
c.2649T>C · rs1417235196 · VCV1534532
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
Conditions
2
Meckel syndrome
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 2 | GERP -3.8, phastCons 1 |
| Overall | ||
| CADD | 6.765 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,179,882 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,613,772 alleles · very rare
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
- RPGRIP1L
- Protein
- p.Pro883=
- Coding
- c.2649T>C
- MANE Select
- NM_015272
- dbSNP
- rs1417235196
- Type
- single nucleotide variant
- Location
- chr16:53645659 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.02 · 1 PDB
- Residue 883
- the c2 2 domain
Similar variants
- RPGRIP1L p.Pro883fs Likely pathogenic ★ same residue
- RPGRIP1L c.1030-1G>T Likely pathogenic ★★ same condition
- RPGRIP1L c.1104-2A>G Likely pathogenic ★★ same condition
- RPGRIP1L c.1243+1G>A Pathogenic/Likely pathogenic ★★ same condition
- RPGRIP1L c.1244-1G>T Likely pathogenic ★★ same condition
- RPGRIP1L c.1582-1G>C Likely pathogenic ★★ same condition
- RPGRIP1L c.1700-1G>A Pathogenic/Likely pathogenic ★★ same condition
- RPGRIP1L c.2152+1G>A Likely pathogenic ★★ same condition
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/rpgrip1l-p-pro883 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown