Is BCORL1 p.Pro262Leu (c.785C>T) pathogenic?

BCORL1 p.Pro262Leu (c.785C>T) is classified Uncertain significance in BCORL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-15). AlphaMissense: likely benign (0.1046); Very rare (popmax 0.000447%, nfe); Associated with Shukla-Vernon syndrome.

What condition is associated with BCORL1 p.Pro262Leu (c.785C>T)?

BCORL1 p.Pro262Leu (c.785C>T) is associated with Shukla-Vernon syndrome (ClinVar).

How common is BCORL1 p.Pro262Leu (c.785C>T) in the general population?

BCORL1 p.Pro262Leu (c.785C>T) is very rare (popmax 0.000447%, nfe) (gnomAD).

What do computational predictors say about BCORL1 p.Pro262Leu (c.785C>T)?

AlphaMissense predicts likely benign (score 0.1046) — an in-silico prediction, not a clinical call.

BCORL1 p.Pro262Leu

c.785C>T · VCV3899863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1046 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Shukla-Vernon syndrome

Computational evidence

Protein change
AlphaMissense	0.1046	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -7.78	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 4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 18 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	17.12	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 0.000447% European (non-Finnish) · 4/895,501 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000455% 5/1,098,046 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0021%	47,638
European (non-Finnish)grpmax	0.000447%	223,875

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BCORL1
Protein: p.Pro262Leu
Coding: c.785C>T
MANE Select: NM_001379451
Type: single nucleotide variant
Location: chrX:130013557 (GRCh38)
Structure: AlphaFold pLDDT 38.79 · 2 PDB

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.Pro262Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BCORL1 p.Pro262Ser 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

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-pro262leu (accessed [today's date]).

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