PGAP3 p.His284=
c.852T>C · VCV3682097
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0112%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.1 | GERP -4.7 |
| Overall | ||
| CADD | 0.067 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0112%
East Asian · 5/44,718 alleles
Filtering AF
0.00436%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00277%
Overall
0.000373%
6/1,609,420 alleles · ultra-rare
exomes 5/1,457,226 · genomes 1/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0112% | 8,944 |
| European (non-Finnish) | 8.49e-05% | 1,178,320 |
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
- PGAP3
- Protein
- p.His284=
- Coding
- c.852T>C
- MANE Select
- NM_033419
- Type
- single nucleotide variant
- Location
- chr17:39673098 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 93.17
- Residue 284
- a UniProt-annotated variant site (found in a patient with toriello-carey syndrome; uncertain significance)
Similar variants
- PGAP3 p.His284Arg Pathogenic/Likely pathogenic ★★ ⚠ same residue
- PGAP3 p.His284Tyr Pathogenic/Likely pathogenic ★★ same residue
- PGAP3 p.His284Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
- PGAP3 c.558-10G>A Pathogenic/Likely pathogenic ★★ same type
- PGAP3 c.694+1G>A Pathogenic ★★ same type
- PGAP3 p.Asp305Gly Pathogenic/Likely pathogenic ★★ same type
- PGAP3 p.Gln89Ter Pathogenic ★★ same type
- PGAP3 p.Glu37Ter 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/pgap3-p-his284 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown