PISD p.Pro175=
c.525G>A · rs368409664 · VCV1645967
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0624%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.047 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -8.1 | GERP -5.3 |
| Overall | ||
| CADD | 8.302 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0624%
East Asian · 28/44,886 alleles
Filtering AF
0.0443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0382%
Overall
0.0039%
63/1,613,710 alleles · ultra-rare
exomes 54/1,461,372 · genomes 9/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0624% | 1,603 |
| Middle Eastern | 0.033% | 3,030 |
| South Asian | 0.00329% | 30,361 |
| African / African-American | 0.00266% | 37,534 |
| European (non-Finnish) | 0.00229% | 43,699 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
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
- PISD
- Protein
- p.Pro175=
- Coding
- c.525G>A
- MANE Select
- NM_001326411
- dbSNP
- rs368409664
- Type
- single nucleotide variant
- Location
- chr22:31621682 (GRCh38)
- Gene constraint
- LOEUF 0.979 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.13
Similar variants
- PISD p.Pro175Thr Uncertain significance ★★ ⚠ same residue
- PISD p.Cys300Tyr Pathogenic/Likely pathogenic ★★ same type
- PISD p.Ala234Val Uncertain significance ★★ ⚠ same type
- PISD p.Ala386Val Uncertain significance ★★ ⚠ same type
- PISD p.Arg125Cys Uncertain significance ★★ ⚠ same type
- PISD p.Arg125His Uncertain significance ★★ ⚠ same type
- PISD p.Arg136His Uncertain significance ★★ ⚠ same type
- PISD p.Arg163Cys 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/pisd-p-pro175 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown