Is BCOR p.Pro1608Thr (c.4822C>A) pathogenic?

BCOR p.Pro1608Thr (c.4822C>A) is classified Uncertain significance in BCOR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-14). AlphaMissense: likely benign (0.2026); Very rare (popmax 0.00693%, nfe); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Pro1608Thr (c.4822C>A)?

BCOR p.Pro1608Thr (c.4822C>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Pro1608Thr (c.4822C>A) in the general population?

BCOR p.Pro1608Thr (c.4822C>A) is very rare (popmax 0.00693%, nfe) (gnomAD).

What do computational predictors say about BCOR p.Pro1608Thr (c.4822C>A)?

AlphaMissense predicts likely benign (score 0.2026) — an in-silico prediction, not a clinical call.

BCOR p.Pro1608Thr

c.4822C>A · rs763713052 · VCV2239921

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2026 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00693%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.2026	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 8.5	GERP 0.61, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	25.7	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 0.00693% European (non-Finnish) · 62/894,854 alleles

Filtering AF 0.00551% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.005%

Overall 0.00602% 66/1,097,113 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00693%	14,433
Remaining individualsnot grpmax-eligible	0.0063%	15,875
Finnishnot grpmax-eligible	0.00214%	46,833

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.Pro1608Thr
Coding: c.4822C>A
MANE Select: NM_001123385
dbSNP: rs763713052
Type: single nucleotide variant
Location: chrX:40054040 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB

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.Pro1608= Benign/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-pro1608thr (accessed [today's date]).

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