Is TRRAP p.Val1908Ile (c.5722G>A) pathogenic?

TRRAP p.Val1908Ile (c.5722G>A) is classified Likely pathogenic in TRRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-27). AlphaMissense: likely pathogenic (0.5787); Absent from gnomAD v4.1.

How common is TRRAP p.Val1908Ile (c.5722G>A) in the general population?

TRRAP p.Val1908Ile (c.5722G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRRAP p.Val1908Ile (c.5722G>A)?

AlphaMissense predicts likely pathogenic (score 0.5787) — an in-silico prediction, not a clinical call.

TRRAP p.Val1908Ile

c.5722G>A · rs2484868223 · VCV2504138

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5787 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.5787	likely pathogenic ✓ concordant with ClinVar
REVEL	0.282	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
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	25.4	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 V1901I vs ClinVar V1908I) — verify the residue.

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.Val1908Ile
Coding: c.5722G>A
MANE Select: NM_001375524
dbSNP: rs2484868223
Type: single nucleotide variant
Location: chr7:98953425 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1908: 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-val1908ile (accessed [today's date]).

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