Is ASPM p.Leu2268fs (c.6802del) pathogenic?

ASPM p.Leu2268fs (c.6802del) is classified Likely pathogenic in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Leu2268fs (c.6802del)?

ASPM p.Leu2268fs (c.6802del) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

ASPM p.Leu2268fs

c.6802del · VCV4081191

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

microcephaly 5, primary, autosomal recessive

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 18 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 0.39, phastCons 0.057

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

Variant & gene context

Gene: ASPM
Protein: p.Leu2268fs
Coding: c.6802del
MANE Select: NM_018136
Type: Deletion
Location: chr1:197102449 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2268: the iq 20 domain; the iq 21 domain

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

Disease context

microcephaly 5, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASPM p.Arg2005fs Pathogenic ★★ same condition
ASPM p.Asn1095fs Likely pathogenic ★★ same condition
ASPM p.Asn324fs Pathogenic/Likely pathogenic ★★ same condition
ASPM p.Asn394fs Pathogenic ★★ same condition
ASPM p.Asp1285fs Pathogenic/Likely pathogenic ★★ same condition
ASPM p.Asp990fs Pathogenic ★★ same condition
ASPM p.Gln2904fs Pathogenic ★★ same condition
ASPM p.Glu2731fs 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-leu2268fs (accessed [today's date]).

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