CHIA p.Leu158=
c.474G>C · rs146460083 · VCV720744
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.5%, 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 -0.074 | GERP 1.9 |
| Overall | ||
| CADD | 5.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.5%
East Asian · 672/44,860 alleles
Filtering AF
1.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.37%
Overall
0.0697%
1,124/1,612,088 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.5% | 67 |
| Remaining individualsnot grpmax-eligible | 0.404% | 248 |
| South Asian | 0.118% | 848 |
| Admixed American | 0.0486% | 2,058 |
| African / African-American | 0.044% | 2,271 |
| Middle Eastern | 0.0165% | 6,044 |
| European (non-Finnish) | 0.00254% | 39,302 |
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
- CHIA
- Protein
- p.Leu158=
- Coding
- c.474G>C
- MANE Select
- NM_201653
- dbSNP
- rs146460083
- Type
- single nucleotide variant
- Location
- chr1:111315429 (GRCh38)
- Gene constraint
- LOEUF 1.063 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.65 · 8 PDB
- Residue 158
- a disulfide bond; the gh18 domain; an α-helix
Similar variants
- CHIA p.Ala295Thr Benign/Likely benign ★★ same type
- CHIA p.Ala57Thr Likely benign ★★ ⚠ same type
- CHIA p.Arg35Trp Benign ★★ ⚠ same type
- CHIA p.Gly317Glu Benign ★★ same type
- CHIA p.Gly356= Benign ★★ same type
- CHIA p.Ile272= Benign ★★ same type
- CHIA p.Lys251= Benign ★★ same type
- CHIA p.Ala182Thr 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/chia-p-leu158 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown