Is BCORL1 p.Pro699Ser (c.2095C>T) pathogenic?

BCORL1 p.Pro699Ser (c.2095C>T) is classified Uncertain significance in BCORL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-01). AlphaMissense: likely benign (0.1067); Absent from gnomAD v4.1.

How common is BCORL1 p.Pro699Ser (c.2095C>T) in the general population?

BCORL1 p.Pro699Ser (c.2095C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCORL1 p.Pro699Ser (c.2095C>T)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

BCORL1 p.Pro699Ser

c.2095C>T · rs996029969 · VCV493547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.346	indeterminate
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 18 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	18.75	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCORL1
Protein: p.Pro699Ser
Coding: c.2095C>T
MANE Select: NM_001379451
dbSNP: rs996029969
Type: single nucleotide variant
Location: chrX:130014867 (GRCh38)
Structure: AlphaFold pLDDT 38.79 · 2 PDB
Residue 699: 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

Similar variants

BCORL1 p.Pro699Leu Uncertain significance ★ ⚠ same residue
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

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-pro699ser (accessed [today's date]).

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