AGPS p.His617=
c.1851T>C · rs1377196070 · VCV1986453
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4 | GERP -5.7 |
| Overall | ||
| CADD | 2.998 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,044 alleles
Filtering AF
0.00211%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000434%
7/1,612,962 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,209 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,440 |
| European (non-Finnish) | 8.48e-05% | 1,179,103 |
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
- AGPS
- Protein
- p.His617=
- Coding
- c.1851T>C
- MANE Select
- NM_003659
- dbSNP
- rs1377196070
- Type
- single nucleotide variant
- Location
- chr2:177523801 (GRCh38)
- Gene constraint
- LOEUF 0.408 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 89.27
- Residue 617
- the 'important for enzyme activity' region
Similar variants
- AGPS p.His617Pro Uncertain significance ⚠ same residue
- AGPS p.Arg182Ter Pathogenic/Likely pathogenic ★★ same type
- AGPS p.Thr309Ile Likely pathogenic ★★ same type
- AGPS c.1855+6C>A Uncertain significance ★★ same type
- AGPS c.*118A>G Uncertain significance ★★ same type
- AGPS p.Arg265Gln Uncertain significance ★★ ⚠ same type
- AGPS p.Asn649Ser Uncertain significance ★★ ⚠ same type
- AGPS p.Asp28Val Uncertain significance ★★ ⚠ 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/agps-p-his617 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown