ASPA c.236+126T>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 41%, eas) — 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 +126 | deep intronic (+126 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.54 | GERP 0.82 |
| Non-coding constraint | Z 3.99 | 1 kb window · o/e 0.72 · regional · uncalibrated |
| Overall | ||
| CADD | 11.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
41%
East Asian · 15,930/38,864 alleles
Filtering AF
40.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 40.2%
Overall
22.4%
198,845/885,826 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 41% | 2 |
| Admixed American | 36.5% | 3 |
| Finnishnot grpmax-eligible | 30.9% | 3 |
| Amishnot grpmax-eligible | 25.7% | 4 |
| Remaining individualsnot grpmax-eligible | 22.1% | 5 |
| South Asian | 21.5% | 5 |
| European (non-Finnish) | 19.9% | 5 |
| African / African-American | 18.6% | 5 |
| Ashkenazi Jewishnot grpmax-eligible | 17.9% | 6 |
| Middle Eastern | 17.7% | 6 |
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
- ASPA
- Coding
- c.236+126T>C
- MANE Select
- NM_000049
- dbSNP
- rs9889588
- Type
- single nucleotide variant
- Location
- chr17:3476521 (GRCh38)
- Gene constraint
- LOEUF 1.098 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.14 · 8 PDB
Similar variants
- ASPA c.236+2T>C Likely pathogenic ★★ same type
- ASPA c.237-1G>T Likely pathogenic ★★ same type
- ASPA c.237-2A>T Pathogenic/Likely pathogenic ★★ same type
- ASPA c.527-1G>A Likely pathogenic ★★ same type
- ASPA c.527-2A>C Likely pathogenic ★★ same type
- ASPA c.527-2A>G Likely pathogenic ★★ same type
- ASPA c.634+1G>T Pathogenic/Likely pathogenic ★★ same type
- ASPA c.635-1G>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/aspa-c-236-plus-126t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown