Is TRRAP p.Val487Leu (c.1459G>T) pathogenic?

TRRAP p.Val487Leu (c.1459G>T) is classified Likely benign in TRRAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-09). AlphaMissense: likely benign (0.1136); Ultra-rare (popmax 0.0162%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRRAP p.Val487Leu (c.1459G>T)?

TRRAP p.Val487Leu (c.1459G>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRRAP p.Val487Leu (c.1459G>T) in the general population?

TRRAP p.Val487Leu (c.1459G>T) is ultra-rare (popmax 0.0162%, nfe) (gnomAD).

What do computational predictors say about TRRAP p.Val487Leu (c.1459G>T)?

AlphaMissense predicts likely benign (score 0.1136) — an in-silico prediction, not a clinical call.

TRRAP p.Val487Leu

c.1459G>T · rs782604679 · VCV2047026

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1136 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0162%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1136	likely benign
REVEL	0.12	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 293 bp · p 0.39 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0162% European (non-Finnish) · 191/1,179,534 alleles

Filtering AF 0.0143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.0125% 201/1,612,176 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0162%	6,176
Remaining individualsnot grpmax-eligible	0.0128%	7,803
Admixed American	0.00334%	29,962

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.Val487Leu
Coding: c.1459G>T
MANE Select: NM_001375524
dbSNP: rs782604679
Type: single nucleotide variant
Location: chr7:98910164 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)

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.Val487Gly Uncertain significance ★ ⚠ 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
TRRAP p.Ala322Ser 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-val487leu (accessed [today's date]).

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