APLF p.Thr442=
c.1326G>A · VCV3413657
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, 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 0.36 | |
| Overall | ||
| CADD | 0.817 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,010 alleles
Filtering AF
0.00687%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.005%
Overall
0.00244%
39/1,598,170 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,010 |
| Admixed American | 0.0139% | 7,186 |
| Remaining individualsnot grpmax-eligible | 0.00809% | 12,357 |
| European (non-Finnish) | 0.00205% | 48,870 |
| South Asian | 0.00113% | 88,284 |
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
- APLF
- Protein
- p.Thr442=
- Coding
- c.1326G>A
- MANE Select
- NM_173545
- Type
- single nucleotide variant
- Location
- chr2:68567380 (GRCh38)
- Gene constraint
- LOEUF 1.451 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.42 · 14 PDB
Similar variants
- APLF p.Thr442Lys Uncertain significance ★ ⚠ same residue
- APLF p.Ala17Pro Uncertain significance ★ ⚠ same type
- APLF p.Ala19Thr Uncertain significance ★ ⚠ same type
- APLF p.Arg10Leu Uncertain significance ★ ⚠ same type
- APLF p.Arg182Lys Uncertain significance ★ ⚠ same type
- APLF p.Arg293Lys Uncertain significance ★ ⚠ same type
- APLF p.Arg418Trp Uncertain significance ★ ⚠ same type
- APLF p.Arg99His 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/aplf-p-thr442 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown