Is BCORL1 p.Ala261Val (c.782C>T) pathogenic?

BCORL1 p.Ala261Val (c.782C>T) is classified Uncertain significance in BCORL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-01). AlphaMissense: likely benign (0.1067); Ultra-rare (popmax 0.0282%, sas).

How common is BCORL1 p.Ala261Val (c.782C>T) in the general population?

BCORL1 p.Ala261Val (c.782C>T) is ultra-rare (popmax 0.0282%, sas) (gnomAD).

What do computational predictors say about BCORL1 p.Ala261Val (c.782C>T)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

BCORL1 p.Ala261Val

c.782C>T · rs143414966 · VCV2333795

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0282%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.82	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 5.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 18 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	14.79	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 0.0282% South Asian · 16/56,738 alleles

Filtering AF 0.0176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0143%

Overall 0.00496% 60/1,208,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0282%	3,546
Remaining individualsnot grpmax-eligible	0.0168%	5,947
European (non-Finnish)	0.00391%	25,571
African / African-American	0.00176%	56,920

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: BCORL1
Protein: p.Ala261Val
Coding: c.782C>T
MANE Select: NM_001379451
dbSNP: rs143414966
Type: single nucleotide variant
Location: chrX:130013554 (GRCh38)
Structure: AlphaFold pLDDT 38.79 · 2 PDB

Full BCORL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCORL1 p.Ala261= Benign ★★ same residue
BCORL1 p.Arg1334Gln Uncertain significance ★★ ⚠ same type
BCORL1 p.Arg1716Gln Uncertain significance ★★ ⚠ same type
BCORL1 p.Asp77Val Uncertain significance ★★ ⚠ same type
BCORL1 p.Gln1076Arg Uncertain significance ★★ ⚠ same type
BCORL1 p.Glu1201Gln Uncertain significance ★★ ⚠ same type
BCORL1 p.Glu1256Asp Uncertain significance ★★ ⚠ same type
BCORL1 p.Glu1744Lys Uncertain significance ★★ ⚠ 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/bcorl1-p-ala261val (accessed [today's date]).

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