NBAS p.Ala1645=
c.4935G>A · rs77299752 · VCV1626926
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.321%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.043 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.8 | GERP -3.5 |
| Overall | ||
| CADD | 0.149 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.321%
East Asian · 144/44,876 alleles
Filtering AF
0.278%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.262%
Overall
0.0344%
556/1,614,162 alleles · rare
exomes 508/1,461,884 · genomes 48/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.321% | 312 |
| Ashkenazi Jewishnot grpmax-eligible | 0.138% | 722 |
| Middle Eastern | 0.0495% | 2,021 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| European (non-Finnish) | 0.0266% | 3,758 |
| Admixed American | 0.025% | 4,002 |
| South Asian | 0.00988% | 10,120 |
| African / African-American | 0.00666% | 15,008 |
| Finnishnot grpmax-eligible | 0.00469% | 21,341 |
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.Ala1645=
- Coding
- c.4935G>A
- MANE Select
- NM_015909
- dbSNP
- rs77299752
- Type
- single nucleotide variant
- Location
- chr2:15292629 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.42
- Residue 1645
- a UniProt-annotated variant site (in ilfs2; uncertain significance); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance; reduced protein expression levels in fibroblasts); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance; reduced collagen secretion; diffuse collagen bundles; reduced protein expression in fibroblasts); the 'interaction with zw10 and rint1' region
Similar variants
- NBAS p.Ala1645Val 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-ala1645 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown