ABCC6 p.Ala158=
c.474G>A · rs376219152 · VCV916431
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0181%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.34 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 17.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0181%
South Asian · 16/88,458 alleles
Filtering AF
0.0113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00923%
Overall
0.00238%
38/1,596,764 alleles · ultra-rare
exomes 34/1,444,750 · genomes 4/152,014 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0181% | 5,529 |
| Admixed American | 0.00855% | 11,699 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00342% | 29,214 |
| Remaining individualsnot grpmax-eligible | 0.00324% | 30,825 |
| East Asian | 0.00224% | 44,546 |
| European (non-Finnish) | 0.00111% | 90,210 |
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
- ABCC6
- Protein
- p.Ala158=
- Coding
- c.474G>A
- MANE Select
- NM_001171
- dbSNP
- rs376219152
- Type
- single nucleotide variant
- Location
- chr16:16219554 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.32 · 4 PDB
- Residue 158
- a UniProt-annotated variant site (in)
Similar variants
- ABCC6 p.Ala158Val Benign/Likely benign ★★ same residue
- ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same type
- ABCC6 c.2071-1G>A Likely pathogenic ★★ same type
- ABCC6 c.2591-1G>T Likely pathogenic ★★ same type
- ABCC6 c.2787+1G>T Pathogenic ★★ same type
- ABCC6 c.3506+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCC6 c.3507-1G>A Pathogenic ★★ same type
- ABCC6 c.3507-2A>G Pathogenic/Likely pathogenic ★★ 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/abcc6-p-ala158 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown