Is BCAS3 p.Ser575fs (c.1723del) pathogenic?

BCAS3 p.Ser575fs (c.1723del) is classified Likely pathogenic in BCAS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-30). Associated with Hengel-Maroofian-Schols syndrome.

What condition is associated with BCAS3 p.Ser575fs (c.1723del)?

BCAS3 p.Ser575fs (c.1723del) is associated with Hengel-Maroofian-Schols syndrome (ClinVar).

BCAS3 p.Ser575fs

c.1723del · VCV4850709

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Hengel-Maroofian-Schols syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP -0.11, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BCAS3
Protein: p.Ser575fs
Coding: c.1723del
MANE Select: NM_017679
Type: Deletion
Location: chr17:61034751 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.25
Residue 575: a UniProt-annotated variant site (in hemars)

Full BCAS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hengel-Maroofian-Schols syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCAS3 c.2594-11434del Uncertain significance ★ same condition
BCAS3 p.Arg544Ter Likely pathogenic ★ same condition
BCAS3 p.Arg636Ter Pathogenic ★ same condition
BCAS3 p.Leu129Ter Likely pathogenic ★ same condition
BCAS3 p.Gly562Arg Uncertain significance ★ ⚠ same condition
BCAS3 p.Ser486Ter Uncertain significance ★ same condition
BCAS3 p.Val219Ile Uncertain significance ★ ⚠ same condition
BCAS3 p.Gln25Ter Pathogenic/Likely pathogenic 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/bcas3-p-ser575fs (accessed [today's date]).

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