Is BCORL1 p.Glu692Lys (c.2074G>A) pathogenic?

BCORL1 p.Glu692Lys (c.2074G>A) is classified Uncertain significance in BCORL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely pathogenic (0.6795); Very rare (popmax 0.000447%, nfe); Associated with BCORL1-related disorder.

What condition is associated with BCORL1 p.Glu692Lys (c.2074G>A)?

BCORL1 p.Glu692Lys (c.2074G>A) is associated with BCORL1-related disorder (ClinVar).

How common is BCORL1 p.Glu692Lys (c.2074G>A) in the general population?

BCORL1 p.Glu692Lys (c.2074G>A) is very rare (popmax 0.000447%, nfe) (gnomAD).

What do computational predictors say about BCORL1 p.Glu692Lys (c.2074G>A)?

AlphaMissense predicts likely pathogenic (score 0.6795) — an in-silico prediction, not a clinical call.

BCORL1 p.Glu692Lys

c.2074G>A · VCV3351841

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6795 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BCORL1-related disorder

Computational evidence

Protein change
AlphaMissense	0.6795	likely pathogenic
REVEL	0.211	benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 18 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	23.6	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 0.000447% European (non-Finnish) · 4/895,442 alleles

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

Overall 0.000364% 4/1,098,212 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.Glu692Lys
Coding: c.2074G>A
MANE Select: NM_001379451
Type: single nucleotide variant
Location: chrX:130014846 (GRCh38)
Structure: AlphaFold pLDDT 38.79 · 2 PDB
Residue 692: 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.Glu692Gly Likely benign ★ same residue
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

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-glu692lys (accessed [today's date]).

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