PYROXD2 p.Ser372=
c.1116G>A · VCV3428792
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0517%, amr)
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 -0.91 | GERP -2.6 |
| Overall | ||
| CADD | 8.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0517%
Admixed American · 31/60,014 alleles
Filtering AF
0.0374%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0325%
Overall
0.00384%
62/1,612,804 alleles · ultra-rare
exomes 37/1,460,602 · genomes 25/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0517% | 1,936 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,245 |
| European (non-Finnish) | 0.00161% | 62,051 |
| African / African-American | 0.00133% | 74,974 |
| South Asian | 0.0011% | 91,042 |
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
- PYROXD2
- Protein
- p.Ser372=
- Coding
- c.1116G>A
- MANE Select
- NM_032709
- Type
- single nucleotide variant
- Location
- chr10:98391029 (GRCh38)
- Gene constraint
- LOEUF 1.145 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.56
Similar variants
- PYROXD2 c.1062+2T>G Uncertain significance ★ same type
- PYROXD2 p.Ala172Asp Uncertain significance ★ ⚠ same type
- PYROXD2 p.Ala293Val Uncertain significance ★ ⚠ same type
- PYROXD2 p.Ala303Ser Uncertain significance ★ ⚠ same type
- PYROXD2 p.Ala312Val Uncertain significance ★ ⚠ same type
- PYROXD2 p.Ala389Val Uncertain significance ★ ⚠ same type
- PYROXD2 p.Ala390Val Uncertain significance ★ ⚠ same type
- PYROXD2 p.Ala524Thr 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/pyroxd2-p-ser372 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown