Is ASPM p.Ser494fs (c.1480del) pathogenic?

ASPM p.Ser494fs (c.1480del) is classified Pathogenic in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). Associated with autosomal recessive primary microcephaly.

What condition is associated with ASPM p.Ser494fs (c.1480del)?

ASPM p.Ser494fs (c.1480del) is associated with autosomal recessive primary microcephaly (ClinVar).

ASPM p.Ser494fs

c.1480del · VCV3902257

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal recessive primary microcephaly

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 3 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 1, phastCons 1

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

Variant & gene context

Gene: ASPM
Protein: p.Ser494fs
Coding: c.1480del
MANE Select: NM_018136
Type: Deletion
Location: chr1:197142772 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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

Disease context

autosomal recessive primary microcephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASPM p.Phe1835fs Pathogenic ★★ same condition
ASPM p.Arg2732fs Pathogenic ★ same condition
ASPM p.Asn1533fs Pathogenic ★ same condition
ASPM p.Val2036fs Pathogenic ★ same condition
ASPM c.2419+2T>C Pathogenic/Likely pathogenic ★★ same condition
ASPM p.Arg1617Ter Pathogenic ★★ same condition
ASPM p.Gln2190Ter Pathogenic ★★ same condition
ASPM p.Gln3060Ter 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/aspm-p-ser494fs (accessed [today's date]).

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