CSTB p.His18=
c.54C>T · rs557717323 · VCV205325
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.201%, afr)
Conditions
2
Inborn genetic diseases
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 0.83 | GERP -4.1, phastCons 0.009 |
| Overall | ||
| CADD | 8.373 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.201%
African / African-American · 144/71,698 alleles
Filtering AF
0.174%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.164%
Overall
0.0108%
166/1,533,076 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.201% | 498 |
| Admixed American | 0.0237% | 4,215 |
| Remaining individualsnot grpmax-eligible | 0.0134% | 7,456 |
| European (non-Finnish) | 0.000175% | 571,611 |
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
- CSTB
- Protein
- p.His18=
- Coding
- c.54C>T
- MANE Select
- NM_000100
- dbSNP
- rs557717323
- Type
- single nucleotide variant
- Location
- chr21:43776216 (GRCh38)
- Gene constraint
- LOEUF 1.681 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 95.81 · 3 PDB
- Residue 18
- an α-helix
Similar variants
- CSTB c.67-1G>C Pathogenic ★★ same condition
- CSTB p.Arg68Ter Pathogenic ★★ same condition
- CSTB p.Gln22Ter Pathogenic/Likely pathogenic ★★ same condition
- CSTB p.Gln46Ter Pathogenic/Likely pathogenic ★★ same condition
- CSTB p.Ala49Thr Uncertain significance ★★ ⚠ same condition
- CSTB p.Ala90Thr Uncertain significance ★★ ⚠ same condition
- CSTB p.Asn52Ile Uncertain significance ★★ ⚠ same condition
- CSTB p.Gln10Glu Uncertain significance ★★ ⚠ same condition
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/cstb-p-his18 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown