Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 52.4%, mid) — 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 0.67 | GERP -4.7, phastCons 0.97 |
| Overall | ||
| CADD | 6.439 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
52.4%
Middle Eastern · 3,171/6,054 alleles
Filtering AF
50.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 50.2%
Overall
34.7%
559,913/1,612,364 alleles · common
exomes 514,010/1,460,248 · genomes 45,903/152,116 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 52.4% | 2 |
| Amishnot grpmax-eligible | 47% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 44.4% | 2 |
| South Asian | 37% | 3 |
| European (non-Finnish) | 36.4% | 3 |
| Remaining individualsnot grpmax-eligible | 35.8% | 3 |
| Finnishnot grpmax-eligible | 31.4% | 3 |
| Admixed American | 24.9% | 4 |
| East Asian | 24.3% | 4 |
| African / African-American | 16.5% | 6 |
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.Leu62=
- Coding
- c.184T>C
- MANE Select
- NM_005050
- dbSNP
- rs2301345
- Type
- single nucleotide variant
- Location
- chr14:74299649 (GRCh38)
- Gene constraint
- LOEUF 0.772 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.18 · 4 PDB
- Residue 62
- 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-leu62 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown