TREM2 p.Phe143=
c.429C>T · rs139397773 · VCV1666503
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
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 0.047 | |
| Overall | ||
| CADD | 2.235 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/59,992 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.0044%
71/1,613,928 alleles · ultra-rare
exomes 59/1,461,806 · genomes 12/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,615 |
| European (non-Finnish) | 0.00466% | 21,455 |
| African / African-American | 0.00267% | 37,453 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
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
- TREM2
- Protein
- p.Phe143=
- Coding
- c.429C>T
- MANE Select
- NM_018965
- dbSNP
- rs139397773
- Type
- single nucleotide variant
- Location
- chr6:41159845 (GRCh38)
- Gene constraint
- LOEUF 1.211 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.85 · 15 PDB
- Residue 143
- a UniProt-annotated variant site (in plosl2; results in decreased osteoclast differentiation; no trem2 transcripts can be detected in patient cells homozygous for the variant); a UniProt-annotated variant site (in plosl2; complete loss of protein expression); a UniProt-annotated variant site (in plosl2)
Similar variants
- TREM2 p.Phe143fs Likely pathogenic ★ same residue
- TREM2 c.483-2A>C Likely pathogenic ★★ same type
- TREM2 p.Asp86Val Likely pathogenic ★★ same type
- TREM2 p.Gln33Ter Pathogenic ★★ same type
- TREM2 p.Thr66Met Pathogenic/Likely pathogenic ★★ same type
- TREM2 p.Val126Gly Pathogenic/Likely pathogenic ★★ same type
- TREM2 c.-51G>A Uncertain significance ★★ same type
- TREM2 c.-98C>T 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/trem2-p-phe143 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown