Is TRRAP p.Pro1825Ser (c.5473C>T) pathogenic?

TRRAP p.Pro1825Ser (c.5473C>T) is classified Likely benign in TRRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-17). AlphaMissense: ambiguous (0.3434); Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with TRRAP p.Pro1825Ser (c.5473C>T)?

TRRAP p.Pro1825Ser (c.5473C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRRAP p.Pro1825Ser (c.5473C>T) in the general population?

TRRAP p.Pro1825Ser (c.5473C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about TRRAP p.Pro1825Ser (c.5473C>T)?

AlphaMissense predicts ambiguous (score 0.3434) — an in-silico prediction, not a clinical call.

TRRAP p.Pro1825Ser

c.5473C>T · VCV3462384

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3434 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3434	ambiguous
REVEL	0.276	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 4,613 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P1818S vs ClinVar P1825S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,884 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000372% 6/1,612,492 alleles · very rare exomes 4/1,460,656 · genomes 2/151,836 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,221
African / African-American	0.00268%	37,367

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.Pro1825Ser
Coding: c.5473C>T
MANE Select: NM_001375524
Type: single nucleotide variant
Location: chr7:98953176 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)

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.Pro1825= Likely benign ★★ 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-pro1825ser (accessed [today's date]).

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