Is THRAP3 p.Arg700Gln (c.2099G>A) pathogenic?

THRAP3 p.Arg700Gln (c.2099G>A) is classified Uncertain significance in THRAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: likely benign (0.1198); Ultra-rare (popmax 0.0164%, mid).

How common is THRAP3 p.Arg700Gln (c.2099G>A) in the general population?

THRAP3 p.Arg700Gln (c.2099G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about THRAP3 p.Arg700Gln (c.2099G>A)?

AlphaMissense predicts likely benign (score 0.1198) — an in-silico prediction, not a clinical call.

THRAP3 p.Arg700Gln

c.2099G>A · VCV3806747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1198 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1198	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 21 kb · p 7.2e-10 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00105% 17/1,613,406 alleles · ultra-rare exomes 13/1,461,334 · genomes 4/152,072 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
African / African-American	0.00267%	37,437
South Asian	0.0022%	45,529
European (non-Finnish)	0.00102%	98,299

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.Arg700Gln
Coding: c.2099G>A
MANE Select: NM_005119
Type: single nucleotide variant
Location: chr1:36293919 (GRCh38)
Gene constraint: LOEUF 0.244 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.40
Residue 700: the 'required for mrna decay activity' region; the 'disordered' 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-arg700gln (accessed [today's date]).

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