Is BCOR p.Ser1271Leu (c.3812C>T) pathogenic?

BCOR p.Ser1271Leu (c.3812C>T) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). AlphaMissense: likely benign (0.0763); Very rare (popmax 0.00529%, sas).

How common is BCOR p.Ser1271Leu (c.3812C>T) in the general population?

BCOR p.Ser1271Leu (c.3812C>T) is very rare (popmax 0.00529%, sas) (gnomAD).

What do computational predictors say about BCOR p.Ser1271Leu (c.3812C>T)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

BCOR p.Ser1271Leu

c.3812C>T · VCV3378076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00529%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.5	GERP 0.68, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,355 bp · p 0.26 · regional, not allelic
Overall
CADD	12.52	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 0.00529% South Asian · 3/56,723 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000689%

Overall 0.000909% 11/1,210,040 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00529%	18,908
African / African-American	0.00349%	28,649
Finnishnot grpmax-eligible	0.00214%	46,671
Remaining individualsnot grpmax-eligible	0.0021%	47,600
European (non-Finnish)	0.000447%	223,748

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.Ser1271Leu
Coding: c.3812C>T
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40063643 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1271: the 'disordered' region

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

Similar variants

BCOR p.Ser1271= Benign/Likely benign ★★ same residue
BCOR p.Arg1163Ter Pathogenic ★★ same type
BCOR p.Arg1164Ter Pathogenic ★★ same type
BCOR p.Arg1217Ter Pathogenic ★★ same type
BCOR p.Arg1514Ter Pathogenic ★★ same type
BCOR p.Arg342Ter Pathogenic ★★ same type
BCOR p.Arg810Ter Pathogenic ★★ same type
BCOR p.Arg976Ter Pathogenic ★★ same type

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-ser1271leu (accessed [today's date]).

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