Is BCOR p.Ser1298Phe (c.3893C>T) pathogenic?

BCOR p.Ser1298Phe (c.3893C>T) is classified Benign/Likely benign in BCOR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-23). AlphaMissense: likely benign (0.1676); Ultra-rare (popmax 0.052%, afr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Ser1298Phe (c.3893C>T)?

BCOR p.Ser1298Phe (c.3893C>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Ser1298Phe (c.3893C>T) in the general population?

BCOR p.Ser1298Phe (c.3893C>T) is ultra-rare (popmax 0.052%, afr) (gnomAD).

What do computational predictors say about BCOR p.Ser1298Phe (c.3893C>T)?

AlphaMissense predicts likely benign (score 0.1676) — an in-silico prediction, not a clinical call.

BCOR p.Ser1298Phe

c.3893C>T · rs749073971 · VCV2904557

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1676 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.052%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.1676	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -8.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,355 bp · p 0.26 · regional, not allelic
Overall
CADD	28.0	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 0.052% African / African-American · 26/49,994 alleles

Filtering AF 0.0364% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.0099% 110/1,111,322 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.052%	1,923
Remaining individualsnot grpmax-eligible	0.0285%	3,511
Admixed American	0.0191%	5,248
European (non-Finnish)	0.00771%	12,970

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.Ser1298Phe
Coding: c.3893C>T
MANE Select: NM_001123385
dbSNP: rs749073971
Type: single nucleotide variant
Location: chrX:40063026 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1298: the 'disordered' region

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.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-ser1298phe (accessed [today's date]).

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