TREM2 p.Asp86=
c.258C>T · rs551003505 · VCV764020
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, eas)
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 -8.6 | |
| Overall | ||
| CADD | 0.032 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
East Asian · 12/44,888 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00347%
56/1,614,238 alleles · ultra-rare
exomes 49/1,461,890 · genomes 7/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0267% | 3,741 |
| South Asian | 0.022% | 4,555 |
| Admixed American | 0.00999% | 10,006 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,837 |
| African / African-American | 0.004% | 25,017 |
| Finnishnot grpmax-eligible | 0.00156% | 64,036 |
| European (non-Finnish) | 0.000932% | 107,277 |
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.Asp86=
- Coding
- c.258C>T
- MANE Select
- NM_018965
- dbSNP
- rs551003505
- Type
- single nucleotide variant
- Location
- chr6:41161396 (GRCh38)
- Gene constraint
- LOEUF 1.211 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.85 · 15 PDB
- Residue 86
- 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); the ig-like v-type domain; a β-strand
Similar variants
- TREM2 p.Asp86Val Likely pathogenic ★★ same residue
- TREM2 p.Asp86fs Pathogenic ★ same residue
- TREM2 c.483-2A>C 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-asp86 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown