Is TRRAP p.Pro513Ala (c.1537C>G) pathogenic?

TRRAP p.Pro513Ala (c.1537C>G) is classified Conflicting classifications of pathogenicity in TRRAP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-25). AlphaMissense: likely benign (0.0605); Very rare (popmax 0.000136%); Associated with Inborn genetic diseases.

What condition is associated with TRRAP p.Pro513Ala (c.1537C>G)?

TRRAP p.Pro513Ala (c.1537C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TRRAP p.Pro513Ala (c.1537C>G) in the general population?

TRRAP p.Pro513Ala (c.1537C>G) is very rare (popmax 0.000136%) (gnomAD).

What do computational predictors say about TRRAP p.Pro513Ala (c.1537C>G)?

AlphaMissense predicts likely benign (score 0.0605) — an in-silico prediction, not a clinical call.

TRRAP p.Pro513Ala

c.1537C>G · rs1797012961 · VCV1720026

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0605 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000136%)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0605	likely benign
REVEL	0.203	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 0.5	GERP -2.7, phastCons 0.056
Regional constraint	o/e 0.92	unconstrained · MANE · 293 bp · p 0.39 · regional, not allelic
Overall
CADD	6.235	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 0.000136%

Overall 0.000136% 2/1,469,736 alleles · very rare

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.Pro513Ala
Coding: c.1537C>G
MANE Select: NM_001375524
dbSNP: rs1797012961
Type: single nucleotide variant
Location: chr7:98910242 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 513: the 'disordered' region

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-pro513ala (accessed [today's date]).

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