PYROXD1 c.414+330C>T
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 63.4%, mid) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +330 | deep intronic (+330 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.77 | GERP -0.63 |
| Overall | ||
| CADD | 0.533 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
63.4%
Middle Eastern · 166/262 alleles
Filtering AF
59.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 58.9%
Overall
56.4%
73,765/130,896 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 63.4% | 2 |
| East Asian | 61.6% | 2 |
| Admixed American | 60.3% | 2 |
| Remaining individualsnot grpmax-eligible | 59% | 2 |
| Amishnot grpmax-eligible | 57.5% | 2 |
| African / African-American | 56.8% | 2 |
| Finnishnot grpmax-eligible | 56.7% | 2 |
| South Asian | 56.6% | 2 |
| European (non-Finnish) | 54.9% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 52% | 2 |
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
- PYROXD1
- Coding
- c.414+330C>T
- MANE Select
- NM_024854
- dbSNP
- rs61926273
- Type
- single nucleotide variant
- Location
- chr12:21450021 (GRCh38)
- Gene constraint
- LOEUF 1.107 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.64 · 2 PDB
Similar variants
- PYROXD1 c.285+1G>A Pathogenic/Likely pathogenic ★★ same type
- PYROXD1 c.881-2A>T Likely pathogenic ★★ same type
- PYROXD1 p.Asn155Ser Pathogenic ★★ same type
- PYROXD1 p.Ala393Val Uncertain significance ★★ ⚠ same type
- PYROXD1 p.Arg132Cys Uncertain significance ★★ ⚠ same type
- PYROXD1 p.Arg455Gln Uncertain significance ★★ ⚠ same type
- PYROXD1 p.Arg76Cys Uncertain significance ★★ ⚠ same type
- PYROXD1 p.Asn52Asp 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/pyroxd1-c-414-plus-330c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown