Is TRAPPC11 p.Arg34Ter (c.100C>T) pathogenic?

TRAPPC11 p.Arg34Ter (c.100C>T) is classified Pathogenic/Likely pathogenic in TRAPPC11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-10). Very rare (popmax 0.00223%, eas); Associated with autosomal recessive limb-girdle muscular dystrophy type R18.

What condition is associated with TRAPPC11 p.Arg34Ter (c.100C>T)?

TRAPPC11 p.Arg34Ter (c.100C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type R18 (ClinVar).

How common is TRAPPC11 p.Arg34Ter (c.100C>T) in the general population?

TRAPPC11 p.Arg34Ter (c.100C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

TRAPPC11 p.Arg34Ter

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.100C>T · rs569565392 · VCV620437

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 30
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000929% 15/1,614,100 alleles · very rare exomes 15/1,461,844 · genomes 0/152,256 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)	0.0011%	90,770

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.Arg34Ter
Coding: c.100C>T
MANE Select: NM_021942
dbSNP: rs569565392
Type: single nucleotide variant
Location: chr4:183663967 (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.Arg34= Likely benign ★ same residue
TRAPPC11 c.1113+2T>G Likely pathogenic ★★ same condition
TRAPPC11 c.1287+5G>A Pathogenic/Likely pathogenic ★★ same condition
TRAPPC11 c.1366+1G>A Likely pathogenic ★★ same condition
TRAPPC11 c.1568-1G>T Pathogenic/Likely pathogenic ★★ same condition
TRAPPC11 p.Arg1065Ter Pathogenic ★★ same condition
TRAPPC11 p.Arg398Ter Pathogenic/Likely pathogenic ★★ same condition
TRAPPC11 p.Arg450Ter Pathogenic/Likely 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-arg34ter (accessed [today's date]).

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