Is BCAS3 p.Ser486Ter (c.1457C>G) pathogenic?

BCAS3 p.Ser486Ter (c.1457C>G) is classified Uncertain significance in BCAS3 (ClinVar, Single submitter, 3 submitters; last evaluated 2018-11-30). Absent from gnomAD v4.1; Associated with Hengel-Maroofian-Schols syndrome.

What condition is associated with BCAS3 p.Ser486Ter (c.1457C>G)?

BCAS3 p.Ser486Ter (c.1457C>G) is associated with Hengel-Maroofian-Schols syndrome (ClinVar).

How common is BCAS3 p.Ser486Ter (c.1457C>G) in the general population?

BCAS3 p.Ser486Ter (c.1457C>G) is absent from gnomAD v4.1 (gnomAD).

BCAS3 p.Ser486Ter

c.1457C>G · rs2145432917 · VCV993269

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Hengel-Maroofian-Schols syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 24
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCAS3
Protein: p.Ser486Ter
Coding: c.1457C>G
MANE Select: NM_017679
dbSNP: rs2145432917
Type: single nucleotide variant
Location: chr17:60990206 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.25
Residue 486: a UniProt-annotated variant site (in hemars); the 'required for recruitment to preautophagosomal structure in response to mitophagy' region; the 'disordered' region

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 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.Val219Ile Uncertain significance ★ ⚠ same condition
BCAS3 p.Gln25Ter Pathogenic/Likely pathogenic same condition
BCAS3 p.Tyr242Ter Pathogenic/Likely pathogenic same condition
BCAS3 p.Ser575fs 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-ser486ter (accessed [today's date]).

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