ALAS2 p.Ala503=
c.1509C>T · rs377127748 · VCV1336744
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0109%, 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 1.1 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 6.832 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0109%
European (non-Finnish) · 98/895,071 alleles
Filtering AF
0.00919%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00844%
Overall
0.00827%
100/1,209,328 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0109% | 9,133 |
| Remaining individualsnot grpmax-eligible | 0.0042% | 23,798 |
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.Ala503=
- Coding
- c.1509C>T
- MANE Select
- NM_000032
- dbSNP
- rs377127748
- Type
- single nucleotide variant
- Location
- chrX:55013577 (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-ala503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown