Is TRRAP p.Arg3255His (c.9764G>A) pathogenic?

TRRAP p.Arg3255His (c.9764G>A) is classified Uncertain significance in TRRAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-02). AlphaMissense: likely pathogenic (0.8428); Very rare (popmax 8.47e-05%, nfe).

How common is TRRAP p.Arg3255His (c.9764G>A) in the general population?

TRRAP p.Arg3255His (c.9764G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about TRRAP p.Arg3255His (c.9764G>A)?

AlphaMissense predicts likely pathogenic (score 0.8428) — an in-silico prediction, not a clinical call.

TRRAP p.Arg3255His

c.9764G>A · rs2485004565 · VCV1723690

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8428 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.8428	likely pathogenic
REVEL	0.558	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 14 kb · p 3.8e-34 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R3259H vs ClinVar R3255H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.84e-05% 1/1,461,872 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: TRRAP
Protein: p.Arg3255His
Coding: c.9764G>A
MANE Select: NM_001375524
dbSNP: rs2485004565
Type: single nucleotide variant
Location: chr7:98992144 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 3255: the fat domain; an α-helix

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

Similar variants

TRRAP p.Arg3255Cys Uncertain significance ★ ⚠ same residue
TRRAP p.Arg3255= Likely benign ★ same residue
TRRAP p.Arg1035Gln Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Glu1104Gly Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Glu1106Lys Likely pathogenic ★★ same type
TRRAP p.Met3318Val Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Val1030Ile Likely pathogenic ★★ same type
TRRAP c.2622+3A>G 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/trrap-p-arg3255his (accessed [today's date]).

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