NBAS p.His1756=
c.5268C>T · rs759123968 · VCV1578755
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0103%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.311 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -7.3 | GERP -5.1 |
| Overall | ||
| CADD | 0.236 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0103%
European (non-Finnish) · 122/1,179,944 alleles
Filtering AF
0.00884%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00828%
Overall
0.00837%
135/1,613,808 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0103% | 9,672 |
| Admixed American | 0.00834% | 11,991 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,825 |
| African / African-American | 0.00267% | 37,444 |
| East Asian | 0.00223% | 44,868 |
| South Asian | 0.0022% | 45,538 |
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.His1756=
- Coding
- c.5268C>T
- MANE Select
- NM_015909
- dbSNP
- rs759123968
- Type
- single nucleotide variant
- Location
- chr2:15276972 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.42
- Residue 1756
- 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 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
- NBAS c.513+2T>C Pathogenic/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-his1756 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown