ALAS2 p.Glu358=
c.1074G>A · rs373739339 · VCV3005240
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00123%, nfe)
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 -0.61 | GERP -2.3, phastCons 0.025 |
| Overall | ||
| CADD | 3.638 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00123%
European (non-Finnish) · 11/894,885 alleles
Filtering AF
0.00066%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000482%
Overall
0.00091%
11/1,208,982 alleles · very rare
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.Glu358=
- Coding
- c.1074G>A
- MANE Select
- NM_000032
- dbSNP
- rs373739339
- Type
- single nucleotide variant
- Location
- chrX:55015672 (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-glu358 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown