Is TRAPPC11 p.Phe899Ser (c.2696T>C) pathogenic?

TRAPPC11 p.Phe899Ser (c.2696T>C) is classified Uncertain significance in TRAPPC11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-21). AlphaMissense: likely pathogenic (0.8593); Ultra-rare (popmax 0.0217%, amr); Associated with autosomal recessive limb-girdle muscular dystrophy type R18.

What condition is associated with TRAPPC11 p.Phe899Ser (c.2696T>C)?

TRAPPC11 p.Phe899Ser (c.2696T>C) is associated with autosomal recessive limb-girdle muscular dystrophy type R18 (ClinVar).

How common is TRAPPC11 p.Phe899Ser (c.2696T>C) in the general population?

TRAPPC11 p.Phe899Ser (c.2696T>C) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about TRAPPC11 p.Phe899Ser (c.2696T>C)?

AlphaMissense predicts likely pathogenic (score 0.8593) — an in-silico prediction, not a clinical call.

TRAPPC11 p.Phe899Ser

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.2696T>C · rs777270916 · VCV474356

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8593 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive limb-girdle muscular dystrophy type R18

Computational evidence

Protein change
AlphaMissense	0.8593	likely pathogenic
REVEL	0.309	indeterminate
SaProt	LLR -9.02	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 49 kb · p 0.0011 · regional, not allelic
Overall
CADD	29.8	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

Grpmax group 0.0217% Admixed American · 13/59,868 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.00112% 18/1,613,750 alleles · ultra-rare exomes 14/1,461,572 · genomes 4/152,178 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,605
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,582
African / African-American	0.00133%	74,908
South Asian	0.0011%	91,048
European (non-Finnish)	0.000169%	589,977

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.Phe899Ser
Coding: c.2696T>C
MANE Select: NM_021942
dbSNP: rs777270916
Type: single nucleotide variant
Location: chr4:183697680 (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 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
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-phe899ser (accessed [today's date]).

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