Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 22.9%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
methylmalonic acidemia with homocystinuria, type cblJ
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 -3.6 | GERP -5.1 |
| Overall | ||
| CADD | 6.818 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
22.9%
African / African-American · 17,171/74,942 alleles
Filtering AF
22.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 22.5%
Overall
1.22%
19,666/1,614,070 alleles · common
exomes 9,836/1,461,886 · genomes 9,830/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 22.9% | 4 |
| Remaining individualsnot grpmax-eligible | 1.59% | 63 |
| Admixed American | 1.49% | 67 |
| Middle Eastern | 1.07% | 93 |
| European (non-Finnish) | 0.0428% | 2,337 |
| South Asian | 0.0417% | 2,397 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| East Asian | 0.00223% | 44,884 |
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
- ABCD4
- Protein
- p.Tyr286=
- Coding
- c.858C>T
- MANE Select
- NM_005050
- dbSNP
- rs1052000
- Type
- single nucleotide variant
- Location
- chr14:74292826 (GRCh38)
- Gene constraint
- LOEUF 0.772 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.18 · 4 PDB
- Residue 286
- the abc transmembrane type-1 domain
Disease context
methylmalonic acidemia with homocystinuria, type cblJ — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Methylmalonic acidemia with homocystinuria (Orphanet):
- Inheritance
- Autosomal recessive, X-linked recessive
- Onset
- All ages
Similar variants
- ABCD4 c.542+1G>T Pathogenic ★★ same condition
- ABCD4 p.Arg432Gln Likely pathogenic ★★ same condition
- ABCD4 p.Asn141Lys Pathogenic/Likely pathogenic ★★ same condition
- ABCD4 p.Gln530Ter Pathogenic/Likely pathogenic ★★ same condition
- ABCD4 p.Tyr176Ter Pathogenic/Likely pathogenic ★★ same condition
- ABCD4 c.1028+5G>A Uncertain significance ★★ same condition
- ABCD4 c.425+6C>T Uncertain significance ★★ same condition
- ABCD4 c.719+6T>C Uncertain significance ★★ 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/abcd4-p-tyr286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown