PITRM1 p.Pro766=
c.2298G>A · rs3740607 · VCV1599799
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 69.6%, eas) — 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. | ||
| REVEL | 0.022 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -8 | GERP -3.4 |
| Overall | ||
| CADD | 0.107 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
69.6%
East Asian · 31,183/44,784 alleles
Filtering AF
69%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 68.7%
Overall
50.9%
815,767/1,603,530 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 69.6% | 1 |
| Admixed American | 60% | 2 |
| Amishnot grpmax-eligible | 55.5% | 2 |
| South Asian | 53.6% | 2 |
| Remaining individualsnot grpmax-eligible | 51.5% | 2 |
| European (non-Finnish) | 49.9% | 2 |
| Middle Eastern | 49.3% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 48.7% | 2 |
| African / African-American | 47.6% | 2 |
| Finnishnot grpmax-eligible | 47.3% | 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.Pro766=
- Coding
- c.2298G>A
- MANE Select
- NM_014889
- dbSNP
- rs3740607
- Type
- single nucleotide variant
- Location
- chr10:3147188 (GRCh38)
- Gene constraint
- LOEUF 0.997 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.44 · 8 PDB
- Residue 766
- an α-helix
Similar variants
- PITRM1 p.Pro766Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro766 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown