PITRM1 p.Ser329=
c.987C>T · rs1055892340 · VCV2866727
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0288%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.26 | donor loss, 20 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.34 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -3.6 | GERP -3.7 |
| Overall | ||
| CADD | 0.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0288%
Admixed American · 17/59,072 alleles
Filtering AF
0.0183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.00156%
25/1,600,278 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0288% | 3,475 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,086 |
| African / African-American | 0.00134% | 74,738 |
| European (non-Finnish) | 0.000512% | 195,133 |
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.Ser329=
- Coding
- c.987C>T
- MANE Select
- NM_014889
- dbSNP
- rs1055892340
- Type
- single nucleotide variant
- Location
- chr10:3159868 (GRCh38)
- Gene constraint
- LOEUF 0.997 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.44 · 8 PDB
- Residue 329
- a disulfide bond; 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-ser329 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown