Is TRAPPC4 p.Arg100Pro (c.299G>C) pathogenic?

TRAPPC4 p.Arg100Pro (c.299G>C) is classified Uncertain significance in TRAPPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: likely pathogenic (0.9215); Ultra-rare (popmax 0.032%, nfe).

How common is TRAPPC4 p.Arg100Pro (c.299G>C) in the general population?

TRAPPC4 p.Arg100Pro (c.299G>C) is ultra-rare (popmax 0.032%, nfe) (gnomAD).

What do computational predictors say about TRAPPC4 p.Arg100Pro (c.299G>C)?

AlphaMissense predicts likely pathogenic (score 0.9215) — an in-silico prediction, not a clinical call.

TRAPPC4 p.Arg100Pro

c.299G>C · rs145384040 · VCV2217617

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9215 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9215	likely pathogenic
REVEL	0.406	indeterminate
SaProt	LLR -4.66	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 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 3,028 bp · p 0.78 · regional, not allelic
Overall
CADD	26.5	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 0.032% European (non-Finnish) · 378/1,180,032 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0283%

Overall 0.0242% 390/1,614,036 alleles · ultra-rare exomes 379/1,461,888 · genomes 11/152,148 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.032%	3,122
Remaining individualsnot grpmax-eligible	0.0128%	7,811
African / African-American	0.00534%	18,729

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.Arg100Pro
Coding: c.299G>C
MANE Select: NM_016146
dbSNP: rs145384040
Type: single nucleotide variant
Location: chr11:119019266 (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.Arg100= Benign ★★ same residue
TRAPPC4 p.Arg100Leu 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-arg100pro (accessed [today's date]).

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