Is TRRAP p.Ala747Val (c.2240C>T) pathogenic?

TRRAP p.Ala747Val (c.2240C>T) is classified Uncertain significance in TRRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely pathogenic (0.9819); Very rare (popmax 0.00167%, amr).

How common is TRRAP p.Ala747Val (c.2240C>T) in the general population?

TRRAP p.Ala747Val (c.2240C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about TRRAP p.Ala747Val (c.2240C>T)?

AlphaMissense predicts likely pathogenic (score 0.9819) — an in-silico prediction, not a clinical call.

TRRAP p.Ala747Val

c.2240C>T · VCV4881307

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9819 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.9819	likely pathogenic
REVEL	0.523	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 7,100 bp · p 9.7e-19 · regional, not allelic
Overall
CADD	29.6	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 0.00167% Admixed American · 1/59,992 alleles

Overall 0.000248% 4/1,614,038 alleles · very rare exomes 3/1,461,848 · genomes 1/152,190 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,932
European (non-Finnish)	8.47e-05%	1,180,011

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.Ala747Val
Coding: c.2240C>T
MANE Select: NM_001375524
Type: single nucleotide variant
Location: chr7:98915763 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 747: an α-helix

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

Similar variants

TRRAP p.Ala747= 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
TRRAP c.7176+4A>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-ala747val (accessed [today's date]).

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