Is TRRAP p.Ala1925Val (c.5774C>T) pathogenic?

TRRAP p.Ala1925Val (c.5774C>T) is classified Uncertain significance in TRRAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-07). AlphaMissense: likely benign (0.0823); Ultra-rare (popmax 0.0126%, nfe).

How common is TRRAP p.Ala1925Val (c.5774C>T) in the general population?

TRRAP p.Ala1925Val (c.5774C>T) is ultra-rare (popmax 0.0126%, nfe) (gnomAD).

What do computational predictors say about TRRAP p.Ala1925Val (c.5774C>T)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

TRRAP p.Ala1925Val

c.5774C>T · rs150693311 · VCV2072895

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0126%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 1,880 bp · p 8.8e-12 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A1918V vs ClinVar A1925V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0126% European (non-Finnish) · 149/1,180,028 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0103%

Overall 0.00985% 159/1,614,194 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0126%	7,920
Remaining individualsnot grpmax-eligible	0.008%	12,500
Admixed American	0.005%	20,011
East Asian	0.00223%	44,886
South Asian	0.0011%	91,082

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.Ala1925Val
Coding: c.5774C>T
MANE Select: NM_001375524
dbSNP: rs150693311
Type: single nucleotide variant
Location: chr7:98955141 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1925: an α-helix; a UniProt-annotated variant site (in)

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

Similar variants

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
TRRAP c.8247+5G>T 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-ala1925val (accessed [today's date]).

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