CHIA p.Lys251=
c.753G>A · rs114510939 · VCV711968
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.25%, afr)
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 -2.2 | GERP -1.1 |
| Overall | ||
| CADD | 1.533 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.25%
African / African-American · 1,687/75,030 alleles
Filtering AF
2.16%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.12%
Overall
0.135%
2,182/1,614,010 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.25% | 44 |
| Middle Eastern | 0.264% | 379 |
| Remaining individualsnot grpmax-eligible | 0.187% | 534 |
| Admixed American | 0.162% | 619 |
| European (non-Finnish) | 0.0221% | 4,521 |
| South Asian | 0.00439% | 22,762 |
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.Lys251=
- Coding
- c.753G>A
- MANE Select
- NM_201653
- dbSNP
- rs114510939
- Type
- single nucleotide variant
- Location
- chr1:111318516 (GRCh38)
- Gene constraint
- LOEUF 1.063 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.65 · 8 PDB
- Residue 251
- 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.Ala182Thr Uncertain significance ★ ⚠ same type
- CHIA p.Ala182Val 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-lys251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown