Is TRIM2 p.Val566= (c.1698G>A) pathogenic?

TRIM2 p.Val566= (c.1698G>A) is classified Likely benign in TRIM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-09). Very rare (popmax 0.00659%, sas); Associated with Charcot-Marie-Tooth disease type 2R.

What condition is associated with TRIM2 p.Val566= (c.1698G>A)?

TRIM2 p.Val566= (c.1698G>A) is associated with Charcot-Marie-Tooth disease type 2R (ClinVar).

How common is TRIM2 p.Val566= (c.1698G>A) in the general population?

TRIM2 p.Val566= (c.1698G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

How is Charcot-Marie-Tooth disease type 2R inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TRIM2 p.Val566=

c.1698G>A · rs747022098 · VCV711178

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

Charcot-Marie-Tooth disease type 2R

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 -5.7	GERP -3.1
Overall
CADD	0.249	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,064 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.0039% 63/1,613,818 alleles · very rare exomes 61/1,461,614 · genomes 2/152,204 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,177
Remaining individualsnot grpmax-eligible	0.0064%	15,617
European (non-Finnish)	0.00432%	23,137
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
African / African-American	0.00133%	74,916

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: TRIM2
Protein: p.Val566=
Coding: c.1698G>A
MANE Select: NM_015271
dbSNP: rs747022098
Type: single nucleotide variant
Location: chr4:153315915 (GRCh38)
Gene constraint: LOEUF 0.398 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.91 · 6 PDB
Residue 566: a β-strand

Full TRIM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 2R — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Charcot-Marie-Tooth disease type 2R (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

TRIM2 p.Ala139Val Uncertain significance ★★ ⚠ same condition
TRIM2 p.Ala174Thr Uncertain significance ★★ ⚠ same condition
TRIM2 p.Ala225Ser Uncertain significance ★★ ⚠ same condition
TRIM2 p.Ala225Thr Uncertain significance ★★ ⚠ same condition
TRIM2 p.Arg166Gln Uncertain significance ★★ ⚠ same condition
TRIM2 p.Arg166Trp Uncertain significance ★★ ⚠ same condition
TRIM2 p.Arg245His Uncertain significance ★★ ⚠ same condition
TRIM2 p.Arg321Gln 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/trim2-p-val566 (accessed [today's date]).

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