Is TRAP1 p.Ala64fs (c.187_190dup) pathogenic?

TRAP1 p.Ala64fs (c.187190dup) is classified Uncertain significance in TRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-23). Ultra-rare (popmax 0.015%, afr).

How common is TRAP1 p.Ala64fs (c.187_190dup) in the general population?

TRAP1 p.Ala64fs (c.187_190dup) is ultra-rare (popmax 0.015%, afr) (gnomAD).

TRAP1 p.Ala64fs

c.187_190dup · VCV3697433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, afr)

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 2 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.3	GERP 1.5, phastCons 1
Overall
CADD	28.3	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 0.015% African / African-American · 11/73,424 alleles

Filtering AF 0.00831% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00645%

Overall 0.000693% 11/1,587,166 alleles · ultra-rare exomes 3/1,434,858 · genomes 8/152,308 · joint denominator

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: TRAP1
Protein: p.Ala64fs
Coding: c.187_190dup
MANE Select: NM_016292
Type: Duplication
Location: chr16:3690883 (GRCh38)
Gene constraint: LOEUF 1.343 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 24 PDB

Full TRAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAP1 p.Ala64Thr Uncertain significance ★★ ⚠ same residue
TRAP1 c.1938_1940+8dup Uncertain significance ★ same type
TRAP1 p.Ser477_Gly478insAla Benign ★ same type
TRAP1 p.Ala191_Glu192insTer Uncertain significance 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/trap1-p-ala64fs (accessed [today's date]).

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