ALAS2 p.Ala66=
c.198G>A · rs137993499 · VCV136357
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.48%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.032 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 5.594 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.48%
African / African-American · 2,561/57,122 alleles
Filtering AF
4.34%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.28%
Overall
0.235%
2,846/1,209,945 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.48% | 22 |
| Remaining individualsnot grpmax-eligible | 0.29% | 345 |
| Admixed American | 0.159% | 628 |
| Middle Eastern | 0.0689% | 1,451 |
| South Asian | 0.0123% | 8,117 |
| European (non-Finnish) | 0.00715% | 13,986 |
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
- ALAS2
- Protein
- p.Ala66=
- Coding
- c.198G>A
- MANE Select
- NM_000032
- dbSNP
- rs137993499
- Type
- single nucleotide variant
- Location
- chrX:55024824 (GRCh38)
- Structure
- AlphaFold pLDDT 82.76 · 27 PDB
Similar variants
- ALAS2 p.Arg170Cys Pathogenic/Likely pathogenic ★★ same type
- ALAS2 p.Arg411Cys Pathogenic ★★ same type
- ALAS2 p.Arg452Cys Pathogenic ★★ same type
- ALAS2 p.Arg452His Pathogenic ★★ ⚠ same type
- ALAS2 p.Arg452Ser Pathogenic ★★ ⚠ same type
- ALAS2 c.1168+4A>C Uncertain significance ★★ same type
- ALAS2 p.Ala282Thr Uncertain significance ★★ ⚠ same type
- ALAS2 p.Ala336Asp 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/alas2-p-ala66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown