NBEA p.Val1997=
c.5991A>G · rs377443545 · VCV2643755
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
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 -2.1 | GERP -4.6 |
| Overall | ||
| CADD | 0.773 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,034 alleles
Filtering AF
0.00123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00105%
Overall
0.00162%
26/1,602,226 alleles · ultra-rare
exomes 22/1,450,084 · genomes 4/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,034 |
| Admixed American | 0.00338% | 29,572 |
| European (non-Finnish) | 0.00188% | 53,319 |
| African / African-American | 0.00134% | 74,596 |
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
- NBEA
- Protein
- p.Val1997=
- Coding
- c.5991A>G
- MANE Select
- NM_001385012
- dbSNP
- rs377443545
- Type
- single nucleotide variant
- Location
- chr13:35349195 (GRCh38)
- Gene constraint
- LOEUF 0.137 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 1997
- a UniProt-annotated variant site (in nedege)
Similar variants
- NBEA p.Arg1299Ter Pathogenic/Likely pathogenic ★★ same type
- NBEA p.Arg145Ter Pathogenic/Likely pathogenic ★★ same type
- NBEA p.Arg2213Ter Pathogenic/Likely pathogenic ★★ same type
- NBEA p.Arg2866Ter Pathogenic ★★ same type
- NBEA p.Arg696Ter Pathogenic/Likely pathogenic ★★ same type
- NBEA p.Asp319Tyr Likely pathogenic ★★ same type
- NBEA c.4242+5G>A Uncertain significance ★★ same type
- NBEA p.Ala603Val 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/nbea-p-val1997 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown