Is TRRAP p.Ala3840Ser (c.11518G>T) pathogenic?

TRRAP p.Ala3840Ser (c.11518G>T) is classified Uncertain significance in TRRAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-30). AlphaMissense: likely benign (0.1074); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with TRRAP p.Ala3840Ser (c.11518G>T)?

TRRAP p.Ala3840Ser (c.11518G>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRRAP p.Ala3840Ser (c.11518G>T) in the general population?

TRRAP p.Ala3840Ser (c.11518G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about TRRAP p.Ala3840Ser (c.11518G>T)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

TRRAP p.Ala3840Ser

c.11518G>T · rs1390624648 · VCV3008061

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.33	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 3,855 bp · p 4.2e-18 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A3826S vs ClinVar A3840S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Overall 0.000137% 2/1,461,760 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,494

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.Ala3840Ser
Coding: c.11518G>T
MANE Select: NM_001375524
dbSNP: rs1390624648
Type: single nucleotide variant
Location: chr7:99012251 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 3840: an α-helix; the fatc domain

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 p.Ala3840Thr Uncertain significance ★ same residue
TRRAP p.Ala3840= Likely benign ★ same residue
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

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-ala3840ser (accessed [today's date]).

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