Is BCOR p.Pro1317Leu (c.3950C>T) pathogenic?

BCOR p.Pro1317Leu (c.3950C>T) is classified Benign in BCOR (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-23). AlphaMissense: likely benign (0.05); Ultra-rare (popmax 0.0917%, eas); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Pro1317Leu (c.3950C>T)?

BCOR p.Pro1317Leu (c.3950C>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Pro1317Leu (c.3950C>T) in the general population?

BCOR p.Pro1317Leu (c.3950C>T) is ultra-rare (popmax 0.0917%, eas) (gnomAD).

What do computational predictors say about BCOR p.Pro1317Leu (c.3950C>T)?

AlphaMissense predicts likely benign (score 0.05) — an in-silico prediction, not a clinical call.

BCOR p.Pro1317Leu

c.3950C>T · rs780412607 · VCV465160

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.05 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0917%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.05	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.41	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 0.79	GERP -3.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,355 bp · p 0.26 · regional, not allelic
Overall
CADD	7.258	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 0.0917% East Asian · 30/32,712 alleles

Filtering AF 0.066% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0572%

Overall 0.00295% 35/1,187,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0917%	1,090
Admixed American	0.00238%	41,975
European (non-Finnish)	0.000453%	220,737

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: BCOR
Protein: p.Pro1317Leu
Coding: c.3950C>T
MANE Select: NM_001123385
dbSNP: rs780412607
Type: single nucleotide variant
Location: chrX:40062969 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1317: the 'disordered' region

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

Disease context

microphthalmia, syndromic 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCOR p.Pro1317= Likely benign ★★ same residue
BCOR p.Arg1163Ter Pathogenic ★★ same condition
BCOR p.Arg1217Ter Pathogenic ★★ same condition
BCOR p.Arg1514Ter Pathogenic ★★ same condition
BCOR p.Arg342Ter Pathogenic ★★ same condition
BCOR p.Arg976Ter Pathogenic ★★ same condition
BCOR p.Ala1262Ser Uncertain significance ★★ ⚠ same condition
BCOR p.Ala1307Pro 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/bcor-p-pro1317leu (accessed [today's date]).

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