ABCC8 c.412+312A>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 44.2%, mid) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +312 | deep intronic (+312 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -8.8 | GERP -4 |
| Overall | ||
| CADD | 0.002 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
44.2%
Middle Eastern · 130/294 alleles
Filtering AF
38%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 36.6%
Overall
31%
47,144/152,032 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 44.2% | 2 |
| East Asian | 38.6% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 34.6% | 3 |
| Remaining individualsnot grpmax-eligible | 34% | 3 |
| European (non-Finnish) | 33.1% | 3 |
| Admixed American | 33.1% | 3 |
| Amishnot grpmax-eligible | 31.2% | 3 |
| African / African-American | 28.1% | 4 |
| Finnishnot grpmax-eligible | 24.5% | 4 |
| South Asian | 21% | 5 |
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
- ABCC8
- Coding
- c.412+312A>C
- MANE Select
- NM_000352
- dbSNP
- rs2237969
- Type
- single nucleotide variant
- Location
- chr11:17469789 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.56 · 8 PDB
Similar variants
- ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same type
- ABCC8 c.1333-1013A>G Pathogenic/Likely pathogenic ★★ same type
- ABCC8 c.148+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCC8 c.148+2T>G Likely pathogenic ★★ same type
- ABCC8 c.1630+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCC8 c.1630+1G>T Pathogenic ★★ same type
- ABCC8 c.1817+1G>C Pathogenic ★★ same type
- ABCC8 c.1817+2T>C 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/abcc8-c-412-plus-312a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown