Is BCORL1 p.Pro352Arg (c.1055C>G) pathogenic?

BCORL1 p.Pro352Arg (c.1055C>G) is classified Uncertain significance in BCORL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-09). AlphaMissense: likely benign (0.2642); Absent from gnomAD v4.1; Associated with Shukla-Vernon syndrome.

What condition is associated with BCORL1 p.Pro352Arg (c.1055C>G)?

BCORL1 p.Pro352Arg (c.1055C>G) is associated with Shukla-Vernon syndrome (ClinVar).

How common is BCORL1 p.Pro352Arg (c.1055C>G) in the general population?

BCORL1 p.Pro352Arg (c.1055C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCORL1 p.Pro352Arg (c.1055C>G)?

AlphaMissense predicts likely benign (score 0.2642) — an in-silico prediction, not a clinical call.

BCORL1 p.Pro352Arg

c.1055C>G · rs1929180944 · VCV1028230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2642 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Shukla-Vernon syndrome

Computational evidence

Protein change
AlphaMissense	0.2642	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -9.97	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 5.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 18 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	19.25	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: BCORL1
Protein: p.Pro352Arg
Coding: c.1055C>G
MANE Select: NM_001379451
dbSNP: rs1929180944
Type: single nucleotide variant
Location: chrX:130013827 (GRCh38)
Structure: AlphaFold pLDDT 38.79 · 2 PDB
Residue 352: the 'disordered' region

Full BCORL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Shukla-Vernon syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCORL1 p.Pro352Leu Uncertain significance ★ ⚠ same residue
BCORL1 p.Arg1334Gln Uncertain significance ★★ ⚠ same condition
BCORL1 p.Arg1716Gln Uncertain significance ★★ ⚠ same condition
BCORL1 p.Lys1425Arg Uncertain significance ★★ ⚠ same condition
BCORL1 p.Met430Val Uncertain significance ★★ ⚠ same condition
BCORL1 p.Pro1155Thr Uncertain significance ★★ ⚠ same condition
BCORL1 p.Pro1681Ser Uncertain significance ★★ ⚠ same condition
BCORL1 p.Pro503Leu 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/bcorl1-p-pro352arg (accessed [today's date]).

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