NBAS p.Ala346=
c.1038G>A · rs542114730 · VCV1573274
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
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 -0.53 | GERP -2.4 |
| Overall | ||
| CADD | 7.225 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,850 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000494%
Overall
0.000372%
6/1,613,892 alleles · very rare
exomes 4/1,461,616 · genomes 2/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,425 |
| African / African-American | 0.004% | 25,012 |
| Admixed American | 0.00167% | 60,014 |
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
- NBAS
- Protein
- p.Ala346=
- Coding
- c.1038G>A
- MANE Select
- NM_015909
- dbSNP
- rs542114730
- Type
- single nucleotide variant
- Location
- chr2:15488939 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.42
- Residue 346
- a UniProt-annotated variant site (in ilfs2; uncertain significance); the 'interaction with use1' region
Similar variants
- NBAS p.Ala346Val Uncertain significance ★★ ⚠ same residue
- NBAS c.1726-2A>G Likely pathogenic ★★ same type
- NBAS c.173-2A>G Likely pathogenic ★★ same type
- NBAS c.209+2T>G Pathogenic/Likely pathogenic ★★ same type
- NBAS c.2423+404G>C Likely pathogenic ★★ same type
- NBAS c.335+1G>C Pathogenic/Likely pathogenic ★★ same type
- NBAS c.4461+2T>C Likely pathogenic ★★ same type
- NBAS c.4583-2A>G Likely 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/nbas-p-ala346 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown