Is TRIM2 p.Thr348= (c.1044C>T) pathogenic?

TRIM2 p.Thr348= (c.1044C>T) is classified Likely benign in TRIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-16). Ultra-rare (popmax 0.0535%, eas); Associated with Charcot-Marie-Tooth disease type 2R.

What condition is associated with TRIM2 p.Thr348= (c.1044C>T)?

TRIM2 p.Thr348= (c.1044C>T) is associated with Charcot-Marie-Tooth disease type 2R (ClinVar).

How common is TRIM2 p.Thr348= (c.1044C>T) in the general population?

TRIM2 p.Thr348= (c.1044C>T) is ultra-rare (popmax 0.0535%, eas) (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.Thr348=

c.1044C>T · rs199866418 · VCV703243

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

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 1.4	GERP 1.9, phastCons 1
Overall
CADD	10.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0535% East Asian · 24/44,854 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00223% 36/1,613,420 alleles · ultra-rare exomes 32/1,461,206 · genomes 4/152,214 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0535%	1,869
Remaining individualsnot grpmax-eligible	0.016%	6,246
South Asian	0.0011%	90,984
European (non-Finnish)	8.48e-05%	1,179,567

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.Thr348=
Coding: c.1044C>T
MANE Select: NM_015271
dbSNP: rs199866418
Type: single nucleotide variant
Location: chr4:153295570 (GRCh38)
Gene constraint: LOEUF 0.398 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.91 · 6 PDB

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.Thr348Ser Uncertain significance ★★ ⚠ same residue
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

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-thr348 (accessed [today's date]).

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