Is BCOR p.Ala165Val (c.494C>T) pathogenic?

BCOR p.Ala165Val (c.494C>T) is classified Likely benign in BCOR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-10). AlphaMissense: likely benign (0.1334); Ultra-rare (popmax 0.0356%, eas); Associated with BCOR-related disorder.

What condition is associated with BCOR p.Ala165Val (c.494C>T)?

BCOR p.Ala165Val (c.494C>T) is associated with BCOR-related disorder (ClinVar).

How common is BCOR p.Ala165Val (c.494C>T) in the general population?

BCOR p.Ala165Val (c.494C>T) is ultra-rare (popmax 0.0356%, eas) (gnomAD).

What do computational predictors say about BCOR p.Ala165Val (c.494C>T)?

AlphaMissense predicts likely benign (score 0.1334) — an in-silico prediction, not a clinical call.

BCOR p.Ala165Val

c.494C>T · VCV3349452

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1334 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BCOR-related disorder

Computational evidence

Protein change
AlphaMissense	0.1334	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.56	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 6.2	GERP 0.51, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,243 bp · p 0.27 · regional, not allelic
Overall
CADD	18.66	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 0.0356% East Asian · 12/33,746 alleles

Filtering AF 0.0205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0161%

Overall 0.0019% 23/1,209,416 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0356%	2,812
South Asian	0.00705%	14,178
Remaining individualsnot grpmax-eligible	0.0042%	23,802
European (non-Finnish)	0.000559%	178,968

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.Ala165Val
Coding: c.494C>T
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40074852 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB

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

Disease context

BCOR-related disorder

Similar variants

BCOR p.Ala165Pro Uncertain significance ★★ ⚠ same residue
BCOR p.Arg1217Ter Pathogenic ★★ same condition
BCOR p.Asp174Asn Uncertain significance ★★ ⚠ same condition
BCOR p.Ile730Leu Uncertain significance ★★ ⚠ same condition
BCOR c.4174-2A>G Likely pathogenic ★ same condition
BCOR p.Glu1052Ter Likely pathogenic ★ same condition
BCOR p.Glu1464Ter Likely pathogenic ★ same condition
BCOR p.Gly86Ter Likely pathogenic ★ 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-ala165val (accessed [today's date]).

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