Is BCOR p.Ser1677Pro (c.5029T>C) pathogenic?

BCOR p.Ser1677Pro (c.5029T>C) is classified Conflicting classifications of pathogenicity in BCOR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-05). AlphaMissense: ambiguous (0.375); Ultra-rare (popmax 0.0123%, sas); Associated with Inborn genetic diseases.

What condition is associated with BCOR p.Ser1677Pro (c.5029T>C)?

BCOR p.Ser1677Pro (c.5029T>C) is associated with Inborn genetic diseases, microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Ser1677Pro (c.5029T>C) in the general population?

BCOR p.Ser1677Pro (c.5029T>C) is ultra-rare (popmax 0.0123%, sas) (gnomAD).

What do computational predictors say about BCOR p.Ser1677Pro (c.5029T>C)?

AlphaMissense predicts ambiguous (score 0.375) — an in-silico prediction, not a clinical call.

BCOR p.Ser1677Pro

c.5029T>C · rs772836203 · VCV2969936

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.375 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.375	ambiguous
REVEL	0.148	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	19.57	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 0.0123% South Asian · 7/56,845 alleles

Filtering AF 0.0057% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00408%

Overall 0.000661% 8/1,209,903 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0123%	8,121
Remaining individualsnot grpmax-eligible	0.0021%	47,593

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.Ser1677Pro
Coding: c.5029T>C
MANE Select: NM_001123385
dbSNP: rs772836203
Type: single nucleotide variant
Location: chrX:40052348 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1677: the 'necessary and sufficient for interaction with pcgf1' region; an α-helix

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.Ser1677Phe Uncertain significance ★ ⚠ same residue
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

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-ser1677pro (accessed [today's date]).

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