ASPH p.Glu591Ter
c.1771G>T · rs2129625655 · VCV1210559
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 22 of 25 |
| Splicing | ||
| SpliceAI | Δ0.32 | acceptor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 42.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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
- ASPH
- Protein
- p.Glu591Ter
- Coding
- c.1771G>T
- MANE Select
- NM_004318
- dbSNP
- rs2129625655
- Type
- single nucleotide variant
- Location
- chr8:61526106 (GRCh38)
- Gene constraint
- LOEUF 1.011 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 72.34 · 43 PDB
- Residue 591
- an α-helix
Similar variants
- ASPH p.Arg735Trp Likely pathogenic ★★ same type
- ASPH p.Tyr565Ter Pathogenic/Likely pathogenic ★★ same type
- ASPH p.Arg425Cys Uncertain significance ★★ ⚠ same type
- ASPH p.Arg753His Uncertain significance ★★ ⚠ same type
- ASPH p.Glu506Val Uncertain significance ★★ same type
- ASPH p.Leu433Arg Uncertain significance ★★ ⚠ same type
- ASPH p.Ser299Asn Uncertain significance ★★ ⚠ same type
- ASPH p.Val214Met 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/asph-p-glu591ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown