Is THRAP3 p.Arg39Pro (c.116G>C) pathogenic?

THRAP3 p.Arg39Pro (c.116G>C) is classified Uncertain significance in THRAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: ambiguous (0.3991); Absent from gnomAD v4.1.

How common is THRAP3 p.Arg39Pro (c.116G>C) in the general population?

THRAP3 p.Arg39Pro (c.116G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about THRAP3 p.Arg39Pro (c.116G>C)?

AlphaMissense predicts ambiguous (score 0.3991) — an in-silico prediction, not a clinical call.

THRAP3 p.Arg39Pro

c.116G>C · VCV4184193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3991	ambiguous
REVEL	0.215	benign-leaning
SaProt	LLR -7.39	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 21 kb · p 7.2e-10 · regional, not allelic
Overall
CADD	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: THRAP3
Protein: p.Arg39Pro
Coding: c.116G>C
MANE Select: NM_005119
Type: single nucleotide variant
Location: chr1:36282679 (GRCh38)
Gene constraint: LOEUF 0.244 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.40
Residue 39: the 'disordered' region; the 'required for mrna splicing activation' region

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

Similar variants

THRAP3 p.Arg39His Uncertain significance ★ ⚠ same residue
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

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-arg39pro (accessed [today's date]).

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