Is TRRAP p.Ala1902Ser (c.5704G>T) pathogenic?

TRRAP p.Ala1902Ser (c.5704G>T) is classified Uncertain significance in TRRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-07). AlphaMissense: ambiguous (0.4862); Very rare (popmax 0.000254%, nfe).

How common is TRRAP p.Ala1902Ser (c.5704G>T) in the general population?

TRRAP p.Ala1902Ser (c.5704G>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about TRRAP p.Ala1902Ser (c.5704G>T)?

AlphaMissense predicts ambiguous (score 0.4862) — an in-silico prediction, not a clinical call.

TRRAP p.Ala1902Ser

c.5704G>T · VCV4896972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4862 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4862	ambiguous
REVEL	0.3	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 1,880 bp · p 8.8e-12 · regional, not allelic
Overall
CADD	26.5	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 A1895S vs ClinVar A1902S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,008 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,460,086 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.Ala1902Ser
Coding: c.5704G>T
MANE Select: NM_001375524
Type: single nucleotide variant
Location: chr7:98953407 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1902: an α-helix

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

Similar variants

TRRAP p.Arg1035Gln Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Glu1104Gly Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Glu1106Lys Likely pathogenic ★★ same type
TRRAP p.Met3318Val Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Val1030Ile Likely pathogenic ★★ same type
TRRAP c.2622+3A>G Uncertain significance ★★ same type
TRRAP c.7176+4A>G Uncertain significance ★★ same type
TRRAP c.8247+5G>T Uncertain significance ★★ same type

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-ala1902ser (accessed [today's date]).

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