ABCD3 p.Thr449=
c.1347G>A · VCV4692221
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0374%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.75 | GERP -5.6 |
| Overall | ||
| CADD | 6.579 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0374%
South Asian · 34/90,934 alleles
Filtering AF
0.0274%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0241%
Overall
0.00248%
40/1,611,892 alleles · ultra-rare
exomes 40/1,459,934 · genomes 0/151,958 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0374% | 2,675 |
| East Asian | 0.00447% | 22,373 |
| Admixed American | 0.00334% | 29,946 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,404 |
| European (non-Finnish) | 8.48e-05% | 1,178,561 |
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
- ABCD3
- Protein
- p.Thr449=
- Coding
- c.1347G>A
- MANE Select
- NM_002858
- Type
- single nucleotide variant
- Location
- chr1:94491208 (GRCh38)
- Gene constraint
- LOEUF 0.484 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 83.39 · 9 PDB
- Residue 449
- the abc transporter domain
Similar variants
- ABCD3 p.Thr449Met Uncertain significance ★ ⚠ same residue
- ABCD3 p.Ala131Thr Uncertain significance ★★ ⚠ same type
- ABCD3 p.Ala3Val Uncertain significance ★★ ⚠ same type
- ABCD3 p.Arg496Cys Uncertain significance ★★ ⚠ same type
- ABCD3 p.Asn12Tyr Uncertain significance ★★ ⚠ same type
- ABCD3 p.Ile225Val Uncertain significance ★★ ⚠ same type
- ABCD3 p.Leu23Val Uncertain significance ★★ ⚠ same type
- ABCD3 p.Leu45Val 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/abcd3-p-thr449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown