ALPI p.Ser448=
c.1344C>T · VCV4960534
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00102%, nfe)
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 -20 | GERP -3.1 |
| Overall | ||
| CADD | 1.608 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00102%
European (non-Finnish) · 12/1,179,160 alleles
Filtering AF
0.000543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000429%
Overall
0.000745%
12/1,610,394 alleles · very rare
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
- ALPI
- Protein
- p.Ser448=
- Coding
- c.1344C>T
- MANE Select
- NM_001631
- Type
- single nucleotide variant
- Location
- chr2:232458903 (GRCh38)
- Gene constraint
- LOEUF 1.163 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.46
Similar variants
- ALPI p.Ala97Thr Uncertain significance ★★ ⚠ same type
- ALPI p.Arg299Ter Uncertain significance ★★ same type
- ALPI p.Gln171Arg Uncertain significance ★★ ⚠ same type
- ALPI p.Glu449Asp Uncertain significance ★★ ⚠ same type
- ALPI p.Leu9Pro Uncertain significance ★★ ⚠ same type
- ALPI p.Pro28Leu Uncertain significance ★★ ⚠ same type
- ALPI p.Arg92Cys Likely benign ★★ ⚠ same type
- ALPI p.Asp248= Likely benign ★★ 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/alpi-p-ser448 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown