AGA p.Arg265His
c.794G>A · rs375663828 · VCV348230
Computational evidence
| Protein change | ||
| AlphaMissense | 0.262 | likely benign |
|---|---|---|
| REVEL | 0.934 | strongly pathogenic-leaning |
| SaProt | LLR -12.05 | damaging |
| ⇒ REVEL and SaProt call this damaging; AlphaMissense does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 11 kb · p 0.64 · regional, not allelic |
| Overall | ||
| CADD | 28.1 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.125% | 799 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,206 |
| Admixed American | 0.0117% | 8,572 |
| European (non-Finnish) | 0.00924% | 10,824 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| Finnishnot grpmax-eligible | 0.00156% | 64,026 |
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
- Protein
- p.Arg265His
- Coding
- c.794G>A
- MANE Select
- NM_000027
- dbSNP
- rs375663828
- Type
- single nucleotide variant
- Location
- chr4:177434394 (GRCh38)
- Gene constraint
- LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.41 · 2 PDB
- Residue 265
- an α-helix
Disease context
aspartylglucosaminuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Aspartylglucosaminuria (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood
- Prevalence
- 1-9 / 1 000 000 (Australia)
Similar variants
- AGA p.Arg265Cys Uncertain significance ★★ ⚠ same residue
- AGA p.Arg265Leu Uncertain significance ★ ⚠ same residue
- AGA p.Arg265= Likely benign ★ same residue
- AGA p.Arg265Pro Uncertain significance ⚠ same residue
- AGA c.127+1G>A Likely pathogenic ★★ same condition
- AGA c.127+1G>T Likely pathogenic ★★ same condition
- AGA c.128-2A>G Pathogenic ★★ same condition
- AGA c.281+1G>T Likely pathogenic ★★ same condition
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-p-arg265his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown