Is TRRAP p.Glu63Gln (c.187G>C) pathogenic?

TRRAP p.Glu63Gln (c.187G>C) is classified Uncertain significance in TRRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: ambiguous (0.417); Very rare (popmax 0.00269%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRRAP p.Glu63Gln (c.187G>C)?

TRRAP p.Glu63Gln (c.187G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRRAP p.Glu63Gln (c.187G>C) in the general population?

TRRAP p.Glu63Gln (c.187G>C) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about TRRAP p.Glu63Gln (c.187G>C)?

AlphaMissense predicts ambiguous (score 0.417) — an in-silico prediction, not a clinical call.

TRRAP p.Glu63Gln

c.187G>C · VCV3462381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.417 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.417	ambiguous
REVEL	0.22	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 29 kb · p 1.3e-20 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,434 alleles

Filtering AF 0.000446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000125% 2/1,605,028 alleles · very rare exomes 0/1,452,998 · genomes 2/152,030 · 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: TRRAP
Protein: p.Glu63Gln
Coding: c.187G>C
MANE Select: NM_001375524
Type: single nucleotide variant
Location: chr7:98890371 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 63: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRRAP c.8247+5G>T Uncertain significance ★★ same condition
TRRAP p.Ala1055Thr Uncertain significance ★★ same condition
TRRAP p.Ala1880Val Uncertain significance ★★ ⚠ same condition
TRRAP p.Ala1895Val Uncertain significance ★★ same condition
TRRAP p.Ala1995Thr Uncertain significance ★★ same condition
TRRAP p.Ala2656Thr Uncertain significance ★★ ⚠ same condition
TRRAP p.Ala322Ser Uncertain significance ★★ ⚠ same condition
TRRAP p.Ala3616Thr 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/trrap-p-glu63gln (accessed [today's date]).

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