Is TRAPPC11 p.Ile995= (c.2985C>A) pathogenic?

TRAPPC11 p.Ile995= (c.2985C>A) is classified Likely benign in TRAPPC11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-20). Very rare (popmax 0.00401%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type R18.

What condition is associated with TRAPPC11 p.Ile995= (c.2985C>A)?

TRAPPC11 p.Ile995= (c.2985C>A) is associated with autosomal recessive limb-girdle muscular dystrophy type R18 (ClinVar).

How common is TRAPPC11 p.Ile995= (c.2985C>A) in the general population?

TRAPPC11 p.Ile995= (c.2985C>A) is very rare (popmax 0.00401%, afr) (gnomAD).

TRAPPC11 p.Ile995=

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.2985C>A · rs901059932 · VCV2718622

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

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.
REVEL	0.077	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.007	GERP 0.5, phastCons 0.45
Overall
CADD	1.705	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,766 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000188% 3/1,598,504 alleles · very rare

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.Ile995=
Coding: c.2985C>A
MANE Select: NM_021942
dbSNP: rs901059932
Type: single nucleotide variant
Location: chr4:183705000 (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-ile995 (accessed [today's date]).

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