Is TRAPPC11 p.Val895Ala (c.2684T>C) pathogenic?

TRAPPC11 p.Val895Ala (c.2684T>C) is classified Uncertain significance in TRAPPC11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely benign (0.3397); Rare (popmax 0.234%, eas); Associated with autosomal recessive limb-girdle muscular dystrophy type R18.

What condition is associated with TRAPPC11 p.Val895Ala (c.2684T>C)?

TRAPPC11 p.Val895Ala (c.2684T>C) is associated with autosomal recessive limb-girdle muscular dystrophy type R18 (ClinVar).

How common is TRAPPC11 p.Val895Ala (c.2684T>C) in the general population?

TRAPPC11 p.Val895Ala (c.2684T>C) is rare (popmax 0.234%, eas) (gnomAD).

What do computational predictors say about TRAPPC11 p.Val895Ala (c.2684T>C)?

AlphaMissense predicts likely benign (score 0.3397) — an in-silico prediction, not a clinical call.

TRAPPC11 p.Val895Ala

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.2684T>C · rs200931036 · VCV474353

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3397 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.234%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive limb-girdle muscular dystrophy type R18

Computational evidence

Protein change
AlphaMissense	0.3397	likely benign
REVEL	0.65	pathogenic-leaning
SaProt	LLR -6.50	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	21.2	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

Grpmax group 0.234% East Asian · 105/44,860 alleles

Filtering AF 0.198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.0068% 109/1,603,666 alleles · rare exomes 102/1,451,346 · genomes 7/152,320 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.234%	427
Admixed American	0.00536%	18,667
Remaining individualsnot grpmax-eligible	0.00161%	62,128

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.Val895Ala
Coding: c.2684T>C
MANE Select: NM_021942
dbSNP: rs200931036
Type: single nucleotide variant
Location: chr4:183697558 (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-val895ala (accessed [today's date]).

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