AGL p.Ser174Phe
c.521C>T · VCV4541316
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9923 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9923 | likely pathogenic ✓ concordant with ClinVar · top 3% in AGL |
|---|---|---|
| REVEL | 0.934 | strongly pathogenic-leaning |
| SaProt | LLR -13.13 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.99 | unconstrained · MANE · 71 kb · p 0.78 · regional, not allelic |
| Overall | ||
| CADD | 27.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- AGL
- Protein
- p.Ser174Phe
- Coding
- c.521C>T
- MANE Select
- NM_000642
- Type
- single nucleotide variant
- Location
- chr1:99864446 (GRCh38)
- Gene constraint
- LOEUF 0.72 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.88 · 1 PDB
- Residue 174
- the 'amylo-1,6-glucosidase' region
Similar variants
- AGL p.Ser174= Likely benign ★ same residue
- AGL c.1283+2T>C Likely pathogenic ★★ same type
- AGL c.1284-1G>A Likely pathogenic ★★ same type
- AGL c.1284-2A>G Likely pathogenic ★★ same type
- AGL c.1423+1G>A Pathogenic ★★ same type
- AGL c.1423+1G>C Pathogenic ★★ same type
- AGL c.1423+1G>T Pathogenic/Likely pathogenic ★★ same type
- AGL c.1612-1G>A 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/agl-p-ser174phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown