Is BCORL1 p.Ala672= (c.2016C>T) pathogenic?

BCORL1 p.Ala672= (c.2016C>T) is classified Likely benign in BCORL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Ultra-rare (popmax 0.0229%, mid).

How common is BCORL1 p.Ala672= (c.2016C>T) in the general population?

BCORL1 p.Ala672= (c.2016C>T) is ultra-rare (popmax 0.0229%, mid) (gnomAD).

BCORL1 p.Ala672=

c.2016C>T · rs370391548 · VCV2661416

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -2.8
Overall
CADD	0.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0229% Middle Eastern · 1/4,376 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0126%

Overall 0.0131% 158/1,209,296 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0229%	4,376
European (non-Finnish)	0.0155%	6,439
South Asian	0.00881%	11,350
Admixed American	0.00875%	11,423
Remaining individualsnot grpmax-eligible	0.0084%	11,899
African / African-American	0.00703%	14,233
East Asian	0.00296%	33,730

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.Ala672=
Coding: c.2016C>T
MANE Select: NM_001379451
dbSNP: rs370391548
Type: single nucleotide variant
Location: chrX:130014788 (GRCh38)
Structure: AlphaFold pLDDT 38.79 · 2 PDB
Residue 672: a UniProt-annotated variant site (found in a sterile man with oligoasthenoteratozoospermia; likely pathogenic; loss of nuclear localization; loss of interaction with skp1)

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

Similar variants

BCORL1 p.Ala261Val Uncertain significance ★★ ⚠ same type
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-ala672 (accessed [today's date]).

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