ABCD1 p.Ala646=
c.1938G>A · rs144996101 · VCV1091056
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00699%, afr)
Conditions
2
Inborn genetic diseases
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 -8.4 | GERP -3.1 |
| Overall | ||
| CADD | 0.052 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00699%
African / African-American · 4/57,232 alleles
Filtering AF
0.00233%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0014%
Overall
0.000834%
10/1,199,089 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00699% | 14,308 |
| East Asian | 0.00301% | 33,258 |
| European (non-Finnish) | 0.000562% | 178,037 |
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
- ABCD1
- Protein
- p.Ala646=
- Coding
- c.1938G>A
- MANE Select
- NM_000033
- dbSNP
- rs144996101
- Type
- single nucleotide variant
- Location
- chrX:153743293 (GRCh38)
- Structure
- AlphaFold pLDDT 81.58 · 14 PDB
- Residue 646
- a UniProt-annotated variant site (in ald); an α-helix; the abc transporter domain
Similar variants
- ABCD1 p.Ala646Val Uncertain significance ★★ ⚠ same residue
- ABCD1 p.Ala646Ser Uncertain significance ★ ⚠ same residue
- ABCD1 c.1635-2A>G Pathogenic ★★ same condition
- ABCD1 c.1781-1G>C Pathogenic ★★ same condition
- ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same condition
- ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCD1 c.1866-1G>C Likely pathogenic ★★ same condition
- ABCD1 c.1866-2A>T Likely pathogenic ★★ same condition
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/abcd1-p-ala646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown