ALG2 c.348+568G>A
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.272%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +568 | deep intronic (+568 nt into the intron) |
|---|---|---|
| SpliceAI | Δ0.78 | donor loss at this position · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 0.002 | |
| Non-coding constraint | Z -0.24 | 1 kb window · o/e 1.02 · regional · uncalibrated |
| Overall | ||
| CADD | 2.617 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.272%
Middle Eastern · 13/4,786 alleles
Filtering AF
0.161%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.127%
Overall
0.00163%
22/1,352,008 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.272% | 368 |
| Remaining individualsnot grpmax-eligible | 0.00217% | 46,008 |
| European (non-Finnish) | 0.000783% | 127,728 |
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
- ALG2
- Coding
- c.348+568G>A
- MANE Select
- NM_033087
- dbSNP
- rs766463570
- Type
- single nucleotide variant
- Location
- chr9:99220979 (GRCh38)
- Gene constraint
- LOEUF 1.408 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.03
Similar variants
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- ALG2 p.Arg129Gln Uncertain significance ★★ ⚠ same type
- ALG2 p.Arg130Gln Uncertain significance ★★ ⚠ same type
- ALG2 p.Arg251His Uncertain significance ★★ ⚠ same type
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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/alg2-c-348-plus-568g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown