Is BCORL1 p.Ser1617= (c.4851G>A) pathogenic?

BCORL1 p.Ser1617= (c.4851G>A) is classified Benign/Likely benign in BCORL1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2022-05-17). Low-frequency (popmax 3.27%, afr); Associated with Shukla-Vernon syndrome.

What condition is associated with BCORL1 p.Ser1617= (c.4851G>A)?

BCORL1 p.Ser1617= (c.4851G>A) is associated with Shukla-Vernon syndrome (ClinVar).

How common is BCORL1 p.Ser1617= (c.4851G>A) in the general population?

BCORL1 p.Ser1617= (c.4851G>A) is low-frequency (popmax 3.27%, afr) (gnomAD).

BCORL1 p.Ser1617=

c.4851G>A · rs35736519 · VCV786711

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.27%, afr)

Conditions

Shukla-Vernon syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.9	GERP -3.5
Overall
CADD	0.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.27% African / African-American · 1,864/57,046 alleles

Filtering AF 3.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.09%

Overall 0.194% 2,348/1,209,002 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.27%	31
Admixed American	0.258%	387
Remaining individualsnot grpmax-eligible	0.237%	421
Middle Eastern	0.115%	869
European (non-Finnish)	0.0272%	3,681
East Asian	0.0089%	11,242
South Asian	0.00352%	28,401

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.Ser1617=
Coding: c.4851G>A
MANE Select: NM_001379451
dbSNP: rs35736519
Type: single nucleotide variant
Location: chrX:130050727 (GRCh38)
Structure: AlphaFold pLDDT 38.79 · 2 PDB
Residue 1617: 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

Disease context

Shukla-Vernon syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCORL1 p.Ser1617Leu Uncertain significance ★ ⚠ same residue
BCORL1 p.Arg1334Gln Uncertain significance ★★ ⚠ same condition
BCORL1 p.Arg1716Gln Uncertain significance ★★ ⚠ same condition
BCORL1 p.Lys1425Arg Uncertain significance ★★ ⚠ same condition
BCORL1 p.Met430Val Uncertain significance ★★ ⚠ same condition
BCORL1 p.Pro1155Thr Uncertain significance ★★ ⚠ same condition
BCORL1 p.Pro1681Ser Uncertain significance ★★ ⚠ same condition
BCORL1 p.Pro503Leu 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/bcorl1-p-ser1617 (accessed [today's date]).

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