ALAS2 p.Ile384=
c.1152C>A · rs1935685338 · VCV2810983
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00176%, sas)
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 0.007 | GERP -3.3, phastCons 0.058 |
| Overall | ||
| CADD | 2.001 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00176%
South Asian · 1/56,738 alleles
Overall
0.000165%
2/1,209,150 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00176% | 56,738 |
| African / African-American | 0.00176% | 56,862 |
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.Ile384=
- Coding
- c.1152C>A
- MANE Select
- NM_000032
- dbSNP
- rs1935685338
- Type
- single nucleotide variant
- Location
- chrX:55015594 (GRCh38)
- Structure
- AlphaFold pLDDT 82.76 · 27 PDB
- Residue 384
- a β-strand
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-ile384 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown