PITRM1 p.Ile952=
c.2856C>T · rs2279219 · VCV2200763
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0893%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.30 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.1 | GERP -3.4 |
| Overall | ||
| CADD | 3.601 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0893%
African / African-American · 67/75,036 alleles
Filtering AF
0.0721%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0659%
Overall
0.00799%
129/1,613,710 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0893% | 1,120 |
| Admixed American | 0.00833% | 12,004 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| European (non-Finnish) | 0.00424% | 23,592 |
| East Asian | 0.00223% | 44,882 |
| South Asian | 0.0022% | 45,540 |
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.Ile952=
- Coding
- c.2856C>T
- MANE Select
- NM_014889
- dbSNP
- rs2279219
- Type
- single nucleotide variant
- Location
- chr10:3138965 (GRCh38)
- Gene constraint
- LOEUF 0.997 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.44 · 8 PDB
- Residue 952
- an α-helix; a UniProt-annotated variant site (in)
Similar variants
- PITRM1 p.Ile952Met Benign ★★ 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-ile952 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown