Is TRAPPC4 p.Val8fs (c.23_24del) pathogenic?

TRAPPC4 p.Val8fs (c.2324del) is classified Likely pathogenic in TRAPPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). Very rare (popmax 0.0022%, nfe); Associated with neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy.

What condition is associated with TRAPPC4 p.Val8fs (c.23_24del)?

TRAPPC4 p.Val8fs (c.23_24del) is associated with neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (ClinVar).

How common is TRAPPC4 p.Val8fs (c.23_24del) in the general population?

TRAPPC4 p.Val8fs (c.23_24del) is very rare (popmax 0.0022%, nfe) (gnomAD).

TRAPPC4 p.Val8fs

c.23_24del · VCV3378415

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Conditions

neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.9	GERP -0.86, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% European (non-Finnish) · 26/1,180,036 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00173% 28/1,614,104 alleles · very rare exomes 26/1,461,872 · genomes 2/152,232 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,386
Admixed American	0.00167%	60,012
South Asian	0.0011%	91,090

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: TRAPPC4
Protein: p.Val8fs
Coding: c.23_24del
MANE Select: NM_016146
Type: Microsatellite
Location: chr11:119018816 (GRCh38)
Gene constraint: LOEUF 1.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.02 · 3 PDB
Residue 8: a β-strand

Full TRAPPC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRAPPC4 c.454+3A>G Pathogenic/Likely pathogenic ★★ same condition
TRAPPC4 p.Leu125Pro Likely pathogenic ★ same condition
TRAPPC4 c.176-3C>T Uncertain significance ★ same condition
TRAPPC4 p.Gly87Asp Uncertain significance ★ ⚠ same condition
TRAPPC4 p.Leu42Val Uncertain significance ★ ⚠ same condition
TRAPPC4 p.Leu64Pro Uncertain significance ★ ⚠ same condition
TRAPPC4 p.Pro93Leu Uncertain significance ★ ⚠ same condition
TRAPPC4 p.Tyr22His Uncertain significance ★ ⚠ 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/trappc4-p-val8fs (accessed [today's date]).

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