Is TRAPPC11 p.Ser858Phe (c.2573C>T) pathogenic?

TRAPPC11 p.Ser858Phe (c.2573C>T) is classified Uncertain significance in TRAPPC11 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-18). AlphaMissense: ambiguous (0.3891); Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy type R18.

What condition is associated with TRAPPC11 p.Ser858Phe (c.2573C>T)?

TRAPPC11 p.Ser858Phe (c.2573C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type R18 (ClinVar).

How common is TRAPPC11 p.Ser858Phe (c.2573C>T) in the general population?

TRAPPC11 p.Ser858Phe (c.2573C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAPPC11 p.Ser858Phe (c.2573C>T)?

AlphaMissense predicts ambiguous (score 0.3891) — an in-silico prediction, not a clinical call.

TRAPPC11 p.Ser858Phe

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.2573C>T · rs2111070444 · VCV1382031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3891 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

autosomal recessive limb-girdle muscular dystrophy type R18

Computational evidence

Protein change
AlphaMissense	0.3891	ambiguous
REVEL	0.289	benign-leaning
SaProt	LLR -12.15	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 49 kb · p 0.0011 · regional, not allelic
Overall
CADD	23.2	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.Ser858Phe
Coding: c.2573C>T
MANE Select: NM_021942
dbSNP: rs2111070444
Type: single nucleotide variant
Location: chr4:183694668 (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.Ser858= Conflicting classifications of pathogenicity ★ 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.Arg34Ter Pathogenic/Likely pathogenic ★★ same condition
TRAPPC11 p.Arg398Ter 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-ser858phe (accessed [today's date]).

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