Is BCORL1 p.Pro312Ser (c.934C>T) pathogenic?

BCORL1 p.Pro312Ser (c.934C>T) is classified Uncertain significance in BCORL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: likely benign (0.1066); Very rare (popmax 0.000112%, nfe); Associated with Shukla-Vernon syndrome.

What condition is associated with BCORL1 p.Pro312Ser (c.934C>T)?

BCORL1 p.Pro312Ser (c.934C>T) is associated with Shukla-Vernon syndrome (ClinVar).

How common is BCORL1 p.Pro312Ser (c.934C>T) in the general population?

BCORL1 p.Pro312Ser (c.934C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about BCORL1 p.Pro312Ser (c.934C>T)?

AlphaMissense predicts likely benign (score 0.1066) — an in-silico prediction, not a clinical call.

BCORL1 p.Pro312Ser

c.934C>T · rs1177045353 · VCV3064373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1066 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Shukla-Vernon syndrome

Computational evidence

Protein change
AlphaMissense	0.1066	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.64	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 2.5	GERP 0.58, phastCons 0.99
Regional constraint	o/e 0.85	unconstrained · MANE · 18 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	16.28	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 0.000112% European (non-Finnish) · 1/893,697 alleles

Overall 0.000897% 1/111,536 alleles · very rare

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.Pro312Ser
Coding: c.934C>T
MANE Select: NM_001379451
dbSNP: rs1177045353
Type: single nucleotide variant
Location: chrX:130013706 (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.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
BCORL1 p.Ser1029Asn 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-pro312ser (accessed [today's date]).

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