Is TRRAP p.Ala522fs (c.1562_1563insT) pathogenic?

TRRAP p.Ala522fs (c.15621563insT) is classified Uncertain significance in TRRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-02). No gnomAD frequency available for this variant; Associated with developmental delay with or without dysmorphic facies and autism.

What condition is associated with TRRAP p.Ala522fs (c.1562_1563insT)?

TRRAP p.Ala522fs (c.1562_1563insT) is associated with developmental delay with or without dysmorphic facies and autism (ClinVar).

How common is TRRAP p.Ala522fs (c.1562_1563insT) in the general population?

TRRAP p.Ala522fs (c.1562_1563insT) is no gnomAD frequency available for this variant (gnomAD).

TRRAP p.Ala522fs

c.1562_1563insT · rs2484713129 · VCV2500916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

developmental delay with or without dysmorphic facies and autism

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 15 of 73
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.7	GERP 1.9, phastCons 1
Region caveats
Repeat context	tandem	(TGCCCC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRRAP
Protein: p.Ala522fs
Coding: c.1562_1563insT
MANE Select: NM_001375524
dbSNP: rs2484713129
Type: Insertion
Location: chr7:98910267 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 522: the 'disordered' region

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

Disease context

developmental delay with or without dysmorphic facies and autism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRRAP p.Ala522_Pro523del Uncertain significance ★ same residue
TRRAP p.Ala522delinsSerSer Uncertain significance ★ same residue
TRRAP p.Ala522= Likely benign ★ same residue
TRRAP p.Arg1035Gln Pathogenic/Likely pathogenic ★★ same condition
TRRAP p.Glu1104Gly Pathogenic/Likely pathogenic ★★ same condition
TRRAP p.Met3318Val Pathogenic/Likely pathogenic ★★ same condition
TRRAP p.Ala1995Thr Uncertain significance ★★ same condition
TRRAP p.Ala3669Val 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-ala522fs (accessed [today's date]).

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