Is TREM2 p.Arg98= (c.292C>A) pathogenic?

TREM2 p.Arg98= (c.292C>A) is classified Likely benign in TREM2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Very rare (popmax 0.00517%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TREM2 p.Arg98= (c.292C>A)?

TREM2 p.Arg98= (c.292C>A) is associated with Inborn genetic diseases (ClinVar).

How common is TREM2 p.Arg98= (c.292C>A) in the general population?

TREM2 p.Arg98= (c.292C>A) is very rare (popmax 0.00517%, nfe) (gnomAD).

TREM2 p.Arg98=

c.292C>A · rs147564421 · VCV1664818

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.52	phastCons 0.008
Overall
CADD	1.827	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00517% European (non-Finnish) · 61/1,180,040 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00384% 62/1,614,104 alleles · very rare exomes 51/1,461,890 · genomes 11/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,345
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Arg98=
Coding: c.292C>A
MANE Select: NM_018965
dbSNP: rs147564421
Type: single nucleotide variant
Location: chr6:41161362 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.85 · 15 PDB
Residue 98: 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

Full TREM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TREM2 p.Arg98Trp Uncertain significance ★★ ⚠ same residue
TREM2 p.Ala180Pro Uncertain significance ★★ ⚠ same condition
TREM2 p.Arg5Gln Uncertain significance ★★ ⚠ same condition
TREM2 p.Leu97Pro Uncertain significance ★★ ⚠ same condition
TREM2 p.Asn99Asp Uncertain significance ★ ⚠ same condition
TREM2 p.Gly145Arg Uncertain significance ★ ⚠ same condition
TREM2 p.His19Asn Uncertain significance ★ ⚠ same condition
TREM2 p.Leu7Phe Uncertain significance ★ ⚠ same condition

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-arg98 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown