HAL c.*227A>C
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000309%, nfe)
Conditions
1
histidinemia
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 -2.5 | GERP -1.9 |
| Non-coding constraint | Z -0.10 | 1 kb window · o/e 1.01 · regional · uncalibrated |
| Overall | ||
| CADD | 0.434 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000309%
European (non-Finnish) · 1/323,282 alleles
Overall
0.000174%
1/576,080 alleles · very rare
exomes 1/423,824 · genomes 0/152,256 · joint denominator
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
- HAL
- Coding
- c.*227A>C
- MANE Select
- NM_002108
- dbSNP
- rs886049900
- Type
- single nucleotide variant
- Location
- chr12:95974005 (GRCh38)
- Gene constraint
- LOEUF 1.213 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.83
Disease context
histidinemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Histidinemia (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Sweden)
Similar variants
- HAL c.*392C>T Uncertain significance ★★ same condition
- HAL p.Arg9Cys Uncertain significance ★★ ⚠ same condition
- HAL p.Asn476Lys Uncertain significance ★★ ⚠ same condition
- HAL p.Glu472Lys Uncertain significance ★★ ⚠ same condition
- HAL p.Gly165Ser Uncertain significance ★★ ⚠ same condition
- HAL p.Leu242Met Uncertain significance ★★ ⚠ same condition
- HAL p.Phe485Leu Uncertain significance ★★ ⚠ same condition
- HAL p.Thr123Met 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/hal-c-star-227a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown