ABCD4 p.His118=
c.354C>T · rs768838020 · VCV388242
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0483%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.208 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP -0.85, phastCons 1 |
| Overall | ||
| CADD | 9.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0483%
South Asian · 44/91,072 alleles
Filtering AF
0.0369%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.033%
Overall
0.00285%
46/1,613,944 alleles · ultra-rare
exomes 42/1,461,766 · genomes 4/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0483% | 2,070 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,238 |
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.His118=
- Coding
- c.354C>T
- MANE Select
- NM_005050
- dbSNP
- rs768838020
- Type
- single nucleotide variant
- Location
- chr14:74298001 (GRCh38)
- Gene constraint
- LOEUF 0.772 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.18 · 4 PDB
- Residue 118
- the abc transmembrane type-1 domain
Similar variants
- ABCD4 p.His118Leu Uncertain significance ★ ⚠ same residue
- ABCD4 p.His118Tyr Uncertain significance ★ ⚠ same residue
- ABCD4 c.542+1G>T Pathogenic ★★ same type
- ABCD4 p.Arg432Gln Likely pathogenic ★★ same type
- ABCD4 p.Asn141Lys Pathogenic/Likely pathogenic ★★ same type
- ABCD4 p.Gln530Ter Pathogenic/Likely pathogenic ★★ same type
- ABCD4 p.Tyr176Ter Pathogenic/Likely pathogenic ★★ same type
- ABCD4 c.1028+5G>A 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/abcd4-p-his118 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown