Is TRAPPC11 p.Arg844Pro (c.2531G>C) pathogenic?

TRAPPC11 p.Arg844Pro (c.2531G>C) is classified Uncertain significance in TRAPPC11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-24). AlphaMissense: likely pathogenic (0.9053); Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy type R18.

What condition is associated with TRAPPC11 p.Arg844Pro (c.2531G>C)?

TRAPPC11 p.Arg844Pro (c.2531G>C) is associated with autosomal recessive limb-girdle muscular dystrophy type R18 (ClinVar).

How common is TRAPPC11 p.Arg844Pro (c.2531G>C) in the general population?

TRAPPC11 p.Arg844Pro (c.2531G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAPPC11 p.Arg844Pro (c.2531G>C)?

AlphaMissense predicts likely pathogenic (score 0.9053) — an in-silico prediction, not a clinical call.

TRAPPC11 p.Arg844Pro

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.2531G>C · rs781082721 · VCV1498080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9053 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive limb-girdle muscular dystrophy type R18

Computational evidence

Protein change
AlphaMissense	0.9053	likely pathogenic
REVEL	0.255	benign-leaning
SaProt	LLR -12.62	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 49 kb · p 0.0011 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRAPPC11
Protein: p.Arg844Pro
Coding: c.2531G>C
MANE Select: NM_021942
dbSNP: rs781082721
Type: single nucleotide variant
Location: chr4:183694626 (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.Arg844Cys Uncertain significance ★★ ⚠ same residue
TRAPPC11 p.Arg844His Uncertain significance ★★ ⚠ same residue
TRAPPC11 p.Arg844Leu Uncertain significance ★ ⚠ same residue
TRAPPC11 p.Arg844Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TRAPPC11 p.Arg844= 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

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-arg844pro (accessed [today's date]).

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