ALAS2 p.Cys276=
c.828C>T · rs73214617 · VCV136352
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0938%, 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 -3.7 | GERP -3.7 |
| Overall | ||
| CADD | 1.353 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0938%
European (non-Finnish) · 839/894,373 alleles
Filtering AF
0.0885%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0864%
Overall
0.0728%
880/1,208,969 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0938% | 1,066 |
| Middle Eastern | 0.0469% | 2,130 |
| Remaining individualsnot grpmax-eligible | 0.0399% | 2,504 |
| South Asian | 0.0176% | 5,678 |
| African / African-American | 0.0105% | 9,528 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00454% | 22,026 |
| Finnishnot grpmax-eligible | 0.00429% | 23,283 |
| Admixed American | 0.00218% | 45,787 |
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.Cys276=
- Coding
- c.828C>T
- MANE Select
- NM_000032
- dbSNP
- rs73214617
- Type
- single nucleotide variant
- Location
- chrX:55017661 (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-cys276 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown