Is TRIM2 p.Ala80Val (c.239C>T) pathogenic?

TRIM2 p.Ala80Val (c.239C>T) is classified Uncertain significance in TRIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-27). AlphaMissense: likely benign (0.1627); Ultra-rare (popmax 0.0132%, sas); Associated with Charcot-Marie-Tooth disease type 2R.

What condition is associated with TRIM2 p.Ala80Val (c.239C>T)?

TRIM2 p.Ala80Val (c.239C>T) is associated with Charcot-Marie-Tooth disease type 2R (ClinVar).

How common is TRIM2 p.Ala80Val (c.239C>T) in the general population?

TRIM2 p.Ala80Val (c.239C>T) is ultra-rare (popmax 0.0132%, 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.

What do computational predictors say about TRIM2 p.Ala80Val (c.239C>T)?

AlphaMissense predicts likely benign (score 0.1627) — an in-silico prediction, not a clinical call.

TRIM2 p.Ala80Val

c.239C>T · rs1314440662 · VCV2437265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1627 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Charcot-Marie-Tooth disease type 2R

Computational evidence

Protein change
AlphaMissense	0.1627	likely benign
REVEL	0.474	indeterminate
SaProt	LLR -6.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 124 kb · p 1.1e-19 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A53V vs ClinVar A80V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% South Asian · 12/91,082 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.000805% 13/1,614,060 alleles · ultra-rare exomes 12/1,461,868 · genomes 1/152,192 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,590
East Asian	0.00223%	44,902

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.Ala80Val
Coding: c.239C>T
MANE Select: NM_015271
dbSNP: rs1314440662
Type: single nucleotide variant
Location: chr4:153275916 (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.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-ala80val (accessed [today's date]).

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