NMBR p.Ile46=
c.138C>T · rs117568543 · VCV711317
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.726%, 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 2.4 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 8.673 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.726%
Middle Eastern · 44/6,062 alleles
Filtering AF
0.556%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.496%
Overall
0.209%
3,367/1,614,058 alleles · rare
exomes 3,062/1,461,876 · genomes 305/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.726% | 138 |
| Finnishnot grpmax-eligible | 0.441% | 227 |
| Remaining individualsnot grpmax-eligible | 0.229% | 437 |
| European (non-Finnish) | 0.228% | 439 |
| Ashkenazi Jewishnot grpmax-eligible | 0.182% | 548 |
| South Asian | 0.0999% | 1,001 |
| Admixed American | 0.0783% | 1,277 |
| African / African-American | 0.024% | 4,167 |
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
- NMBR
- Protein
- p.Ile46=
- Coding
- c.138C>T
- MANE Select
- NM_002511
- dbSNP
- rs117568543
- Type
- single nucleotide variant
- Location
- chr6:142088521 (GRCh38)
- Gene constraint
- LOEUF 1.08 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.77 · 2 PDB
- Residue 46
- an α-helix
Similar variants
- NMBR p.Arg310Trp Likely benign ★★ same type
- NMBR p.Ser358= Likely benign ★★ same type
- NMBR p.Ala136Asp Uncertain significance ★ ⚠ same type
- NMBR p.Ala179Val Uncertain significance ★ ⚠ same type
- NMBR p.Ala185Val Uncertain significance ★ ⚠ same type
- NMBR p.Ala236Thr Uncertain significance ★ ⚠ same type
- NMBR p.Ala32Gly Uncertain significance ★ ⚠ same type
- NMBR p.Ala369Val 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/nmbr-p-ile46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown