Is TRRAP p.Ala1043Val (c.3128C>T) pathogenic?

TRRAP p.Ala1043Val (c.3128C>T) is classified Pathogenic in TRRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-16). AlphaMissense: likely pathogenic (0.6568); Absent from gnomAD v4.1; Associated with developmental delay with or without dysmorphic facies and autism.

What condition is associated with TRRAP p.Ala1043Val (c.3128C>T)?

TRRAP p.Ala1043Val (c.3128C>T) is associated with developmental delay with or without dysmorphic facies and autism (ClinVar).

How common is TRRAP p.Ala1043Val (c.3128C>T) in the general population?

TRRAP p.Ala1043Val (c.3128C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRRAP p.Ala1043Val (c.3128C>T)?

AlphaMissense predicts likely pathogenic (score 0.6568) — an in-silico prediction, not a clinical call.

TRRAP p.Ala1043Val

c.3128C>T · rs1790093579 · VCV870465

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6568 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

developmental delay with or without dysmorphic facies and autism

Computational evidence

Protein change
AlphaMissense	0.6568	likely pathogenic ✓ concordant with ClinVar
REVEL	0.232	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.09	constrained · MANE · 71 bp · p 7.3e-08 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRRAP
Protein: p.Ala1043Val
Coding: c.3128C>T
MANE Select: NM_001375524
dbSNP: rs1790093579
Type: single nucleotide variant
Location: chr7:98927319 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1043: an α-helix; a UniProt-annotated variant site (in deddfa)

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.Ala1043Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
TRRAP p.Ala1043= 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
TRRAP p.Ala3764Val 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-ala1043val (accessed [today's date]).

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