PITRM1 p.Pro227=
c.681T>C · rs4609511 · VCV1546009
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 72.6%, nfe) — 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 | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.79 | GERP -3.4 |
| Overall | ||
| CADD | 0.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
72.6%
European (non-Finnish) · 855,133/1,177,856 alleles
Filtering AF
72.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 72.4%
Overall
70.2%
1,129,906/1,610,610 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 72.6% | 1 |
| South Asian | 70.7% | 1 |
| Amishnot grpmax-eligible | 69.3% | 1 |
| Finnishnot grpmax-eligible | 68.6% | 1 |
| Remaining individualsnot grpmax-eligible | 67.7% | 1 |
| East Asian | 59.3% | 2 |
| Middle Eastern | 58.8% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 58.2% | 2 |
| African / African-American | 57.7% | 2 |
| Admixed American | 56.1% | 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
- PITRM1
- Protein
- p.Pro227=
- Coding
- c.681T>C
- MANE Select
- NM_014889
- dbSNP
- rs4609511
- Type
- single nucleotide variant
- Location
- chr10:3163835 (GRCh38)
- Gene constraint
- LOEUF 0.997 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.44 · 8 PDB
- Residue 227
- a disulfide bond
Similar variants
- PITRM1 p.Thr931Met Pathogenic/Likely pathogenic ★★ same type
- PITRM1 p.Ala1003Thr Uncertain significance ★★ ⚠ same type
- PITRM1 p.Ala559Val Uncertain significance ★★ ⚠ same type
- PITRM1 p.Ala887Val Uncertain significance ★★ ⚠ same type
- PITRM1 p.Ala942Val Uncertain significance ★★ ⚠ same type
- PITRM1 p.Ala965Thr Uncertain significance ★★ ⚠ same type
- PITRM1 p.Arg32Trp Uncertain significance ★★ ⚠ same type
- PITRM1 p.Arg545Gln 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/pitrm1-p-pro227 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown