Is EXOSC3 p.Arg73Pro (c.218G>C) pathogenic?

EXOSC3 p.Arg73Pro (c.218G>C) is classified Uncertain significance in EXOSC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely pathogenic (0.6082); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EXOSC3 p.Arg73Pro (c.218G>C)?

EXOSC3 p.Arg73Pro (c.218G>C) is associated with Inborn genetic diseases (ClinVar).

How common is EXOSC3 p.Arg73Pro (c.218G>C) in the general population?

EXOSC3 p.Arg73Pro (c.218G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EXOSC3 p.Arg73Pro (c.218G>C)?

AlphaMissense predicts likely pathogenic (score 0.6082) — an in-silico prediction, not a clinical call.

EXOSC3 p.Arg73Pro

c.218G>C · rs759096213 · VCV3091193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6082 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6082	likely pathogenic
REVEL	0.434	indeterminate
SaProt	LLR -7.87	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 5.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 4,362 bp · p 0.097 · regional, not allelic
Overall
CADD	27.4	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: EXOSC3
Protein: p.Arg73Pro
Coding: c.218G>C
MANE Select: NM_016042
dbSNP: rs759096213
Type: single nucleotide variant
Location: chr9:37784827 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.26 · 8 PDB
Residue 73: a β-strand

Full EXOSC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EXOSC3 p.Arg73= Likely benign ★★ same residue
EXOSC3 p.Ala2Val Uncertain significance ★★ ⚠ same condition
EXOSC3 p.Cys83Gly Uncertain significance ★★ ⚠ same condition
EXOSC3 p.Ser262Leu Uncertain significance ★★ ⚠ same condition
EXOSC3 p.Ser6Cys Uncertain significance ★★ ⚠ same condition
EXOSC3 p.Ser6Phe Uncertain significance ★★ ⚠ same condition
EXOSC3 p.Thr150Ala Uncertain significance ★★ ⚠ same condition
EXOSC3 p.Val131Ala Uncertain significance ★★ ⚠ same condition

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/exosc3-p-arg73pro (accessed [today's date]).

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