Is BCORL1 p.Pro649= (c.1947C>T) pathogenic?

BCORL1 p.Pro649= (c.1947C>T) is classified Likely benign in BCORL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Ultra-rare (popmax 0.0861%, afr); Associated with BCORL1-related disorder.

What condition is associated with BCORL1 p.Pro649= (c.1947C>T)?

BCORL1 p.Pro649= (c.1947C>T) is associated with BCORL1-related disorder (ClinVar).

How common is BCORL1 p.Pro649= (c.1947C>T) in the general population?

BCORL1 p.Pro649= (c.1947C>T) is ultra-rare (popmax 0.0861%, afr) (gnomAD).

BCORL1 p.Pro649=

c.1947C>T · rs148645627 · VCV3045074

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0861%, afr)

Conditions

BCORL1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.247	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.1
Overall
CADD	0.065	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0861% African / African-American · 49/56,931 alleles

Filtering AF 0.0668% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.06%

Overall 0.0148% 179/1,209,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0861%	1,162
Remaining individualsnot grpmax-eligible	0.021%	4,758
European (non-Finnish)	0.013%	7,715
Admixed American	0.00876%	11,414

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.Pro649=
Coding: c.1947C>T
MANE Select: NM_001379451
dbSNP: rs148645627
Type: single nucleotide variant
Location: chrX:130014719 (GRCh38)
Structure: AlphaFold pLDDT 38.79 · 2 PDB
Residue 649: a UniProt-annotated variant site (found in a sterile man with oligoasthenoteratozoospermia; likely pathogenic; loss of nuclear localization; loss of interaction with skp1)

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

Disease context

BCORL1-related disorder

Similar variants

BCORL1 p.Ala1074Thr Uncertain significance ★ ⚠ same condition
BCORL1 p.Arg630Leu Uncertain significance ★ ⚠ same condition
BCORL1 p.Ser1520Gly Uncertain significance ★ ⚠ same condition
BCORL1 p.Ser416Asn Uncertain significance ★ ⚠ same condition
BCORL1 p.Val1491Ala Uncertain significance ★ same condition
BCORL1 p.Arg1278Cys Uncertain significance ⚠ same condition
BCORL1 p.Gln538His Uncertain significance ⚠ same condition
BCORL1 p.Gln838His 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-pro649 (accessed [today's date]).

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