PITRM1 p.Arg75=
c.223A>C · rs767590298 · VCV2044687
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.115%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.80 | donor loss, 1 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.25 | GERP 0.4 |
| Overall | ||
| CADD | 3.888 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.115%
Middle Eastern · 7/6,080 alleles
Filtering AF
0.054%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0383%
Overall
0.00478%
77/1,611,472 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.115% | 869 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,599 |
| European (non-Finnish) | 0.00534% | 18,710 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,514 |
| South Asian | 0.00221% | 45,191 |
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.Arg75=
- Coding
- c.223A>C
- MANE Select
- NM_014889
- dbSNP
- rs767590298
- Type
- single nucleotide variant
- Location
- chr10:3166979 (GRCh38)
- Gene constraint
- LOEUF 0.997 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.44 · 8 PDB
- Residue 75
- a β-strand
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-arg75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown