ALPP p.Phe331=
c.993C>T · rs199688634 · VCV778047
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.28%, mid)
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 | |
| Overall | ||
| CADD | 0.928 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.28%
Middle Eastern · 77/6,026 alleles
Filtering AF
1.23%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.23%
Overall
1.03%
16,624/1,611,454 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.28% | 78 |
| European (non-Finnish) | 1.25% | 80 |
| Remaining individualsnot grpmax-eligible | 0.978% | 102 |
| Admixed American | 0.727% | 138 |
| Finnishnot grpmax-eligible | 0.428% | 234 |
| South Asian | 0.297% | 337 |
| African / African-American | 0.22% | 455 |
| Ashkenazi Jewishnot grpmax-eligible | 0.169% | 592 |
| Amishnot grpmax-eligible | 0.11% | 912 |
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
- ALPP
- Protein
- p.Phe331=
- Coding
- c.993C>T
- MANE Select
- NM_001632
- dbSNP
- rs199688634
- Type
- single nucleotide variant
- Location
- chr2:232380750 (GRCh38)
- Gene constraint
- LOEUF 1.117 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.73 · 8 PDB
- Residue 331
- a β-strand
Similar variants
- ALPP c.865+8C>T Likely benign ★★ same type
- ALPP p.Ala176= Benign ★★ same type
- ALPP p.Arg231Pro Benign ★★ same type
- ALPP p.Arg36= Benign ★★ same type
- ALPP p.Glu37Gln Benign ★★ same type
- ALPP p.Gly233= Likely benign ★★ same type
- ALPP p.Gly63= Likely benign ★★ same type
- ALPP p.Ser192Trp 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/alpp-p-phe331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown