Is THRAP3 p.Val598Asp (c.1793T>A) pathogenic?

THRAP3 p.Val598Asp (c.1793T>A) is classified Uncertain significance in THRAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-15). AlphaMissense: likely pathogenic (0.9985); Very rare (popmax 8.47e-05%, nfe).

How common is THRAP3 p.Val598Asp (c.1793T>A) in the general population?

THRAP3 p.Val598Asp (c.1793T>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about THRAP3 p.Val598Asp (c.1793T>A)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

THRAP3 p.Val598Asp

c.1793T>A · VCV3968558

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9985 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9985	likely pathogenic · top 2% in THRAP3
REVEL	0.564	indeterminate
SaProt	LLR -6.26	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 21 kb · p 7.2e-10 · regional, not allelic
Overall
CADD	27.3	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,018 alleles

Overall 6.2e-05% 1/1,614,166 alleles · very rare exomes 1/1,461,880 · genomes 0/152,286 · joint denominator

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: THRAP3
Protein: p.Val598Asp
Coding: c.1793T>A
MANE Select: NM_005119
Type: single nucleotide variant
Location: chr1:36291421 (GRCh38)
Gene constraint: LOEUF 0.244 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.40
Residue 598: the 'required for mrna decay activity' region

Full THRAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

THRAP3 c.2647-17A>G Likely benign ★★ same type
THRAP3 p.Ala117Ser Uncertain significance ★ ⚠ same type
THRAP3 p.Ala236Val Uncertain significance ★ ⚠ same type
THRAP3 p.Ala291Val Uncertain significance ★ ⚠ same type
THRAP3 p.Ala581Thr Uncertain significance ★ ⚠ same type
THRAP3 p.Arg153Gln Uncertain significance ★ ⚠ same type
THRAP3 p.Arg156His Uncertain significance ★ ⚠ same type
THRAP3 p.Arg15Cys 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/thrap3-p-val598asp (accessed [today's date]).

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