Is BCOR p.Ala25Val (c.74C>T) pathogenic?

BCOR p.Ala25Val (c.74C>T) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-13). AlphaMissense: likely benign (0.0799); Very rare (popmax 0.00217%, amr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Ala25Val (c.74C>T)?

BCOR p.Ala25Val (c.74C>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Ala25Val (c.74C>T) in the general population?

BCOR p.Ala25Val (c.74C>T) is very rare (popmax 0.00217%, amr) (gnomAD).

What do computational predictors say about BCOR p.Ala25Val (c.74C>T)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

BCOR p.Ala25Val

c.74C>T · VCV4488288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -5.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.96	donor gain · deltas
Pangolin	Δ0.59	gain · loss 0.13 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.6	GERP 0.53, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,243 bp · p 0.27 · regional, not allelic
Overall
CADD	32.0	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 0.00217% Admixed American · 1/46,113 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000638% 7/1,097,320 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00217%	46,113
African / African-American	0.00173%	57,940
European (non-Finnish)	0.000559%	178,966

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.Ala25Val
Coding: c.74C>T
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40077856 (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

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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-ala25val (accessed [today's date]).

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