Is BCOR p.Val679Ile (c.2035G>A) pathogenic?

BCOR p.Val679Ile (c.2035G>A) is classified Conflicting classifications of pathogenicity in BCOR (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.1725); Rare (popmax 0.115%, mid); Associated with microphthalmia, syndromic 1.

What condition is associated with BCOR p.Val679Ile (c.2035G>A)?

BCOR p.Val679Ile (c.2035G>A) is associated with microphthalmia, syndromic 1, microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Val679Ile (c.2035G>A) in the general population?

BCOR p.Val679Ile (c.2035G>A) is rare (popmax 0.115%, mid) (gnomAD).

What do computational predictors say about BCOR p.Val679Ile (c.2035G>A)?

AlphaMissense predicts likely benign (score 0.1725) — an in-silico prediction, not a clinical call.

BCOR p.Val679Ile

c.2035G>A · rs144722432 · VCV210518

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1725 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 1

Computational evidence

Protein change
AlphaMissense	0.1725	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.90	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 4.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,116 bp · p 0.013 · regional, not allelic
Overall
CADD	22.6	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 0.115% Middle Eastern · 5/4,350 alleles

Filtering AF 0.0957% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0936%

Overall 0.0829% 1,002/1,208,652 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	870
European (non-Finnish)	0.101%	988
Admixed American	0.0944%	1,060
Remaining individualsnot grpmax-eligible	0.0547%	1,829
Finnishnot grpmax-eligible	0.03%	3,333
Ashkenazi Jewishnot grpmax-eligible	0.0136%	7,329
African / African-American	0.0104%	9,590

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.Val679Ile
Coding: c.2035G>A
MANE Select: NM_001123385
dbSNP: rs144722432
Type: single nucleotide variant
Location: chrX:40073311 (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 1 — 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.Arg976Ter Pathogenic ★★ same condition
BCOR p.Ala1262Ser Uncertain significance ★★ ⚠ same condition
BCOR p.Ala1307Pro Uncertain significance ★★ ⚠ same condition
BCOR p.Ala165Pro 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-val679ile (accessed [today's date]).

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