Is TRAPPC4 p.Arg100= (c.300G>A) pathogenic?

TRAPPC4 p.Arg100= (c.300G>A) is classified Benign in TRAPPC4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-06). Common (popmax 5.67%, afr) — too common for a highly-penetrant pathogenic allele.

TRAPPC4 p.Arg100=

Q: How common is TRAPPC4 p.Arg100= (c.300G>A) in the general population?

TRAPPC4 p.Arg100= (c.300G>A) is common (popmax 5.67%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.300G>A · rs7114591 · VCV1244899

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.67%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.77	GERP -0.81
Overall
CADD	7.571	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.67% African / African-American · 4,252/75,018 alleles

Filtering AF 5.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.47%

Overall 0.297% 4,793/1,614,100 alleles · common exomes 2,419/1,461,876 · genomes 2,374/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.67%	18
Remaining individualsnot grpmax-eligible	0.432%	232
Middle Eastern	0.413%	242
Admixed American	0.275%	364
South Asian	0.0373%	2,679
European (non-Finnish)	0.00398%	25,107

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.Arg100=
Coding: c.300G>A
MANE Select: NM_016146
dbSNP: rs7114591
Type: single nucleotide variant
Location: chr11:119019267 (GRCh38)
Gene constraint: LOEUF 1.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.02 · 3 PDB
Residue 100: an α-helix

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

Similar variants

TRAPPC4 p.Arg100Leu Uncertain significance ★ ⚠ same residue
TRAPPC4 p.Arg100Pro Uncertain significance ★ ⚠ same residue
TRAPPC4 c.454+3A>G Pathogenic/Likely pathogenic ★★ same type
TRAPPC4 c.176-31C>G Benign ★★ same type
TRAPPC4 c.176-40C>G Benign ★★ same type
TRAPPC4 c.176-43C>T Benign ★★ same type
TRAPPC4 c.350+129T>C Benign ★★ same type
TRAPPC4 c.350+58C>T Benign ★★ same type

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-arg100 (accessed [today's date]).

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