ALG8 c.174+238T>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 7.39%, afr) — 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 +238 | deep intronic (+238 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.83 | |
| Overall | ||
| CADD | 4.355 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.39%
African / African-American · 3,062/41,434 alleles
Filtering AF
7.17%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.08%
Overall
2.11%
3,209/152,010 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 7.39% | 14 |
| Remaining individualsnot grpmax-eligible | 1.19% | 84 |
| Admixed American | 0.682% | 147 |
| Middle Eastern | 0.34% | 294 |
| European (non-Finnish) | 0.025% | 4,000 |
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
- ALG8
- Coding
- c.174+238T>C
- MANE Select
- NM_024079
- dbSNP
- rs188432893
- Type
- single nucleotide variant
- Location
- chr11:78127120 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.07
Similar variants
- ALG8 c.368+2T>G Likely pathogenic ★★ same type
- ALG8 c.674-2A>G Likely pathogenic ★★ same type
- ALG8 c.777+1G>A Likely pathogenic ★★ same type
- ALG8 c.95+1G>A Likely pathogenic ★★ same type
- ALG8 p.Arg179Ter Pathogenic/Likely pathogenic ★★ same type
- ALG8 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same type
- ALG8 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same type
- ALG8 p.Arg364Ter 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/alg8-c-174-plus-238t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown