ABCD4 c.719+21C>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +21 | near-intronic (+21 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.17 | GERP -3.5, phastCons 0.008 |
| Non-coding constraint | Z 2.11 | 1 kb window · o/e 0.86 · regional · uncalibrated |
| Overall | ||
| CADD | 1.047 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,060 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0038%
Overall
0.0049%
79/1,613,868 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,030 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,811 |
| Admixed American | 0.00833% | 12,003 |
| European (non-Finnish) | 0.00526% | 19,029 |
| African / African-American | 0.00267% | 37,520 |
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
- Coding
- c.719+21C>A
- MANE Select
- NM_005050
- Type
- single nucleotide variant
- Location
- chr14:74295127 (GRCh38)
- Gene constraint
- LOEUF 0.772 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.18 · 4 PDB
Similar variants
- 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
- ABCD4 c.425+6C>T Uncertain significance ★★ same type
- ABCD4 c.719+6T>C 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-c-719-plus-21c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown