Is BTRC p.Pro593Arg (c.1778C>G) pathogenic?

BTRC p.Pro593Arg (c.1778C>G) is classified Uncertain significance in BTRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-13). AlphaMissense: likely benign (0.1069); Absent from gnomAD v4.1.

How common is BTRC p.Pro593Arg (c.1778C>G) in the general population?

BTRC p.Pro593Arg (c.1778C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTRC p.Pro593Arg (c.1778C>G)?

AlphaMissense predicts likely benign (score 0.1069) — an in-silico prediction, not a clinical call.

BTRC p.Pro593Arg

c.1778C>G · rs775941333 · VCV2483062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1069 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1069	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.69	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 5.9	GERP 1.5, phastCons 1
Regional constraint	o/e 1.41	unconstrained · MANE · 94 bp · p 0.0094 · regional, not allelic
Overall
CADD	17.64	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

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: BTRC
Protein: p.Pro593Arg
Coding: c.1778C>G
MANE Select: NM_033637
dbSNP: rs775941333
Type: single nucleotide variant
Location: chr10:101550820 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.33 · 15 PDB

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

Similar variants

BTRC p.Pro593His Uncertain significance ★ ⚠ same residue
BTRC p.Pro593Leu Uncertain significance ★ ⚠ same residue
BTRC p.Leu271Phe Uncertain significance ★★ ⚠ same type
BTRC p.Leu86Phe Uncertain significance ★★ ⚠ same type
BTRC c.556+7C>G Benign ★★ same type
BTRC p.Ala543Ser Benign ★★ same type
BTRC p.Ile229= Benign ★★ same type
BTRC p.Leu387= Likely benign ★★ 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/btrc-p-pro593arg (accessed [today's date]).

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