Is BCOR p.Thr1644Ile (c.4931C>T) pathogenic?

BCOR p.Thr1644Ile (c.4931C>T) is classified Benign/Likely benign in BCOR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.1446); Rare (popmax 0.121%, amr); Associated with Inborn genetic diseases.

What condition is associated with BCOR p.Thr1644Ile (c.4931C>T)?

BCOR p.Thr1644Ile (c.4931C>T) is associated with Inborn genetic diseases, microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Thr1644Ile (c.4931C>T) in the general population?

BCOR p.Thr1644Ile (c.4931C>T) is rare (popmax 0.121%, amr) (gnomAD).

What do computational predictors say about BCOR p.Thr1644Ile (c.4931C>T)?

AlphaMissense predicts likely benign (score 0.1446) — an in-silico prediction, not a clinical call.

BCOR p.Thr1644Ile

c.4931C>T · rs780610123 · VCV701345

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1446 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1446	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.94	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 0.03	GERP -3.2, phastCons 0.47
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	8.526	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 0.121% Admixed American · 55/45,622 alleles

Filtering AF 0.0951% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0859%

Overall 0.00463% 56/1,209,120 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.121%	829
Remaining individualsnot grpmax-eligible	0.0021%	47,579

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.Thr1644Ile
Coding: c.4931C>T
MANE Select: NM_001123385
dbSNP: rs780610123
Type: single nucleotide variant
Location: chrX:40053931 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1644: the 'necessary and sufficient for interaction with pcgf1' region; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microphthalmia, syndromic 2

Similar variants

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.Arg810Ter 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-thr1644ile (accessed [today's date]).

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