NRL p.Pro34=
c.102C>T · rs201256212 · VCV1545002
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.115%, mid)
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 0.37 | GERP -2.8, phastCons 0.82 |
| Overall | ||
| CADD | 4.817 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.115%
Middle Eastern · 7/6,062 alleles
Filtering AF
0.0542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0384%
Overall
0.000743%
12/1,614,212 alleles · rare
exomes 12/1,461,868 · genomes 0/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.115% | 866 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| South Asian | 0.0011% | 91,086 |
| European (non-Finnish) | 0.000169% | 590,023 |
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
- NRL
- Protein
- p.Pro34=
- Coding
- c.102C>T
- MANE Select
- NM_001354768
- dbSNP
- rs201256212
- Type
- single nucleotide variant
- Location
- chr14:24082747 (GRCh38)
- Gene constraint
- LOEUF 1.917 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.42
- Residue 34
- the 'disordered' region; the 'minimal transactivation domain (mtd)' region
Similar variants
- NRL p.Arg31Ter Pathogenic/Likely pathogenic ★★ same type
- NRL p.Pro51Leu Pathogenic/Likely pathogenic ★★ same type
- NRL p.Pro51Ser Pathogenic/Likely pathogenic ★★ same type
- NRL p.Pro51Thr Pathogenic/Likely pathogenic ★★ same type
- NRL p.Ser50Leu Pathogenic/Likely pathogenic ★★ same type
- NRL p.Ser50Pro Pathogenic/Likely pathogenic ★★ same type
- NRL p.Tyr113Ter Pathogenic/Likely pathogenic ★★ same type
- NRL c.381+3G>C 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/nrl-p-pro34 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown