Is THRAP3 p.Phe73Ile (c.217T>A) pathogenic?

THRAP3 p.Phe73Ile (c.217T>A) is classified Uncertain significance in THRAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely pathogenic (0.988); Absent from gnomAD v4.1.

How common is THRAP3 p.Phe73Ile (c.217T>A) in the general population?

THRAP3 p.Phe73Ile (c.217T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about THRAP3 p.Phe73Ile (c.217T>A)?

AlphaMissense predicts likely pathogenic (score 0.988) — an in-silico prediction, not a clinical call.

THRAP3 p.Phe73Ile

c.217T>A · VCV3456260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.988	likely pathogenic · top 9% in THRAP3
REVEL	0.249	benign-leaning
SaProt	LLR -10.20	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
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	24.7	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.Phe73Ile
Coding: c.217T>A
MANE Select: NM_005119
Type: single nucleotide variant
Location: chr1:36286447 (GRCh38)
Gene constraint: LOEUF 0.244 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.40
Residue 73: 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 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-phe73ile (accessed [today's date]).

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