AGA c.622+252del
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 4.81%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +252 | deep intronic (+252 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.9 | GERP 1.5 |
| Non-coding constraint | Z 2.22 | 1 kb window · o/e 0.83 · regional · uncalibrated |
| Overall | ||
| CADD | 1.461 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.81%
Admixed American · 1,257/26,122 alleles
Filtering AF
4.59%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.5%
Overall
0.721%
3,233/448,638 alleles · low-frequency
exomes 2,057/296,332 · genomes 1,176/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 4.81% | 21 |
| Ashkenazi Jewishnot grpmax-eligible | 3.39% | 29 |
| East Asian | 1.37% | 73 |
| Remaining individualsnot grpmax-eligible | 0.909% | 110 |
| Finnishnot grpmax-eligible | 0.885% | 113 |
| South Asian | 0.728% | 137 |
| European (non-Finnish) | 0.18% | 557 |
| African / African-American | 0.164% | 610 |
| Middle Eastern | 0.135% | 743 |
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
- AGA
- Coding
- c.622+252del
- MANE Select
- NM_000027
- dbSNP
- rs145523464
- Type
- Deletion
- Location
- chr4:177437153 (GRCh38)
- Gene constraint
- LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.41 · 2 PDB
Similar variants
- AGA p.Ala19fs Pathogenic ★★ same type
- AGA p.Asn110fs Pathogenic/Likely pathogenic ★★ same type
- AGA p.Cys64fs Pathogenic/Likely pathogenic ★★ same type
- AGA p.Glu199fs Likely pathogenic ★★ same type
- AGA p.Ile112fs Pathogenic/Likely pathogenic ★★ same type
- AGA p.Lys288_Val289insTer Pathogenic/Likely pathogenic ★★ same type
- AGA p.Thr123fs Pathogenic/Likely pathogenic ★★ same type
- AGA p.Thr125_Leu126insTer 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/aga-c-622-plus-252del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown