ABCC6 p.Ser398=
c.1194C>T · rs376518465 · VCV1672805
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00579%, nfe)
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 -1.6 | GERP -2.3 |
| Overall | ||
| CADD | 2.356 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00579%
European (non-Finnish) · 68/1,174,712 alleles
Filtering AF
0.00464%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00424%
Overall
0.00443%
71/1,603,156 alleles · very rare
exomes 65/1,450,950 · genomes 6/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00579% | 17,275 |
| African / African-American | 0.00267% | 37,391 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,062 |
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.Ser398=
- Coding
- c.1194C>T
- MANE Select
- NM_001171
- dbSNP
- rs376518465
- Type
- single nucleotide variant
- Location
- chr16:16198165 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.32 · 4 PDB
- Residue 398
- the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (in pxe)
Similar variants
- ABCC6 p.Ser398Ile Uncertain significance ★★ ⚠ same residue
- ABCC6 p.Ser398Arg Likely pathogenic ⚠ same residue
- ABCC6 p.Ser398Gly Pathogenic ⚠ 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
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-ser398 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown