Is TRRAP p.Pro1292Ser (c.3874C>T) pathogenic?

TRRAP p.Pro1292Ser (c.3874C>T) is classified Uncertain significance in TRRAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-31). AlphaMissense: likely pathogenic (0.9936); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRRAP p.Pro1292Ser (c.3874C>T)?

TRRAP p.Pro1292Ser (c.3874C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRRAP p.Pro1292Ser (c.3874C>T) in the general population?

TRRAP p.Pro1292Ser (c.3874C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRRAP p.Pro1292Ser (c.3874C>T)?

AlphaMissense predicts likely pathogenic (score 0.9936) — an in-silico prediction, not a clinical call.

TRRAP p.Pro1292Ser

c.3874C>T · rs2484789514 · VCV2527123

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9936 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9936	likely pathogenic
REVEL	0.34	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 37 bp · p 5.3e-05 · regional, not allelic
Overall
CADD	23.5	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.Pro1292Ser
Coding: c.3874C>T
MANE Select: NM_001375524
dbSNP: rs2484789514
Type: single nucleotide variant
Location: chr7:98933262 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1292: a turn

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.Pro1292Thr Likely pathogenic ★ 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-pro1292ser (accessed [today's date]).

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