ALG8 c.368+261G>C
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.65%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +261 | deep intronic (+261 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.36 | GERP -1 |
| Overall | ||
| CADD | 6.539 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.65%
European (non-Finnish) · 1,120/68,028 alleles
Filtering AF
1.57%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.53%
Overall
0.951%
1,448/152,282 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.65% | 61 |
| Finnishnot grpmax-eligible | 0.773% | 129 |
| Admixed American | 0.641% | 156 |
| Amishnot grpmax-eligible | 0.548% | 182 |
| Remaining individualsnot grpmax-eligible | 0.38% | 263 |
| Middle Eastern | 0.34% | 294 |
| South Asian | 0.29% | 345 |
| African / African-American | 0.284% | 352 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0576% | 1,735 |
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.368+261G>C
- MANE Select
- NM_024079
- dbSNP
- rs117628372
- Type
- single nucleotide variant
- Location
- chr11:78123760 (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-368-plus-261g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown