Is TRAPPC11 p.Val124fs (c.370del) pathogenic?

TRAPPC11 p.Val124fs (c.370del) is classified Pathogenic in TRAPPC11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-20). Very rare (popmax 8.48e-05%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type R18.

What condition is associated with TRAPPC11 p.Val124fs (c.370del)?

TRAPPC11 p.Val124fs (c.370del) is associated with autosomal recessive limb-girdle muscular dystrophy type R18 (ClinVar).

How common is TRAPPC11 p.Val124fs (c.370del) in the general population?

TRAPPC11 p.Val124fs (c.370del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

TRAPPC11 p.Val124fs

Q: How is TRAPPC11-related limb-girdle muscular dystrophy R18 inherited?

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

c.370del · rs2477083128 · VCV2135671

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

autosomal recessive limb-girdle muscular dystrophy type R18

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 30
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.2	GERP -3.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,532 alleles

Overall 6.84e-05% 1/1,461,068 alleles · very rare

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: TRAPPC11
Protein: p.Val124fs
Coding: c.370del
MANE Select: NM_021942
dbSNP: rs2477083128
Type: Deletion
Location: chr4:183666422 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.76

Full TRAPPC11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type R18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For TRAPPC11-related limb-girdle muscular dystrophy R18 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

TRAPPC11 p.Glu430_Ile431insTer Pathogenic ★★ same condition
TRAPPC11 p.Phe1058fs Pathogenic/Likely pathogenic ★★ same condition
TRAPPC11 p.Ser171fs Pathogenic/Likely pathogenic ★★ same condition
TRAPPC11 c.1208-14del Likely benign ★★ same condition
TRAPPC11 c.661-13del Benign/Likely benign ★★ same condition
TRAPPC11 c.661-3del Benign ★★ same condition
TRAPPC11 p.Arg725fs Pathogenic ★ same condition
TRAPPC11 p.Asn242fs Pathogenic ★ 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/trappc11-p-val124fs (accessed [today's date]).

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