PGAP3 p.Cys256=
c.768C>T · rs369578650 · VCV2889439
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0232%, 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 -0.32 | GERP -4.7 |
| Overall | ||
| CADD | 11.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0232%
East Asian · 10/43,108 alleles
Filtering AF
0.0126%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0095%
Overall
0.00152%
24/1,578,296 alleles · ultra-rare
exomes 15/1,426,172 · genomes 9/152,124 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0232% | 4,311 |
| African / African-American | 0.0108% | 9,280 |
| South Asian | 0.00463% | 21,618 |
| Admixed American | 0.00188% | 53,306 |
| European (non-Finnish) | 8.6e-05% | 1,162,816 |
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.Cys256=
- Coding
- c.768C>T
- MANE Select
- NM_033419
- dbSNP
- rs369578650
- Type
- single nucleotide variant
- Location
- chr17:39673182 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 93.17
Similar variants
- PER1 p.Glu256Gln Uncertain significance ★ ⚠ 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
- PGAP3 p.His284Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
- PGAP3 p.His284Tyr Pathogenic/Likely 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-cys256 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown