Is BCORL1 p.Pro810Ser (c.2428C>T) pathogenic?

BCORL1 p.Pro810Ser (c.2428C>T) is classified Uncertain significance in BCORL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.0768); Very rare (popmax 0.00701%, sas).

How common is BCORL1 p.Pro810Ser (c.2428C>T) in the general population?

BCORL1 p.Pro810Ser (c.2428C>T) is very rare (popmax 0.00701%, sas) (gnomAD).

What do computational predictors say about BCORL1 p.Pro810Ser (c.2428C>T)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

BCORL1 p.Pro810Ser

c.2428C>T · rs760397145 · VCV1314325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00701%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.87	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 2.7	GERP -2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 18 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	12.44	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 0.00701% South Asian · 4/57,049 alleles

Filtering AF 0.00233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.000364% 4/1,098,122 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.Pro810Ser
Coding: c.2428C>T
MANE Select: NM_001379451
dbSNP: rs760397145
Type: single nucleotide variant
Location: chrX:130015200 (GRCh38)
Structure: AlphaFold pLDDT 38.79 · 2 PDB
Residue 810: 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.Pro810Arg 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-pro810ser (accessed [today's date]).

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