Is BCORL1 p.Pro378Ser (c.1132C>T) pathogenic?

BCORL1 p.Pro378Ser (c.1132C>T) is classified Uncertain significance in BCORL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-31). AlphaMissense: ambiguous (0.3996); Very rare (popmax 9.48e-05%).

How common is BCORL1 p.Pro378Ser (c.1132C>T) in the general population?

BCORL1 p.Pro378Ser (c.1132C>T) is very rare (popmax 9.48e-05%) (gnomAD).

What do computational predictors say about BCORL1 p.Pro378Ser (c.1132C>T)?

AlphaMissense predicts ambiguous (score 0.3996) — an in-silico prediction, not a clinical call.

BCORL1 p.Pro378Ser

c.1132C>T · rs1253901089 · VCV1303228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.48e-05%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3996	ambiguous
REVEL	0.051	moderately benign-leaning
SaProt	LLR -7.62	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 18 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	19.47	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

Grpmax group 9.48e-05%

Overall 9.48e-05% 1/1,054,961 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.Pro378Ser
Coding: c.1132C>T
MANE Select: NM_001379451
dbSNP: rs1253901089
Type: single nucleotide variant
Location: chrX:130013904 (GRCh38)
Structure: AlphaFold pLDDT 38.79 · 2 PDB

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

Similar variants

BCORL1 p.Ala261Val Uncertain significance ★★ ⚠ same type
BCORL1 p.Arg1334Gln Uncertain significance ★★ ⚠ same type
BCORL1 p.Arg1716Gln Uncertain significance ★★ ⚠ same type
BCORL1 p.Asp77Val Uncertain significance ★★ ⚠ same type
BCORL1 p.Gln1076Arg Uncertain significance ★★ ⚠ same type
BCORL1 p.Glu1201Gln Uncertain significance ★★ ⚠ same type
BCORL1 p.Glu1256Asp Uncertain significance ★★ ⚠ same type
BCORL1 p.Glu1744Lys Uncertain significance ★★ ⚠ 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/bcorl1-p-pro378ser (accessed [today's date]).

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