Is ASPM p.Arg2732fs (c.8195_8196del) pathogenic?

ASPM p.Arg2732fs (c.81958196del) is classified Pathogenic in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-11). Very rare (popmax 8.48e-05%, nfe); Associated with autosomal recessive primary microcephaly.

What condition is associated with ASPM p.Arg2732fs (c.8195_8196del)?

ASPM p.Arg2732fs (c.8195_8196del) is associated with autosomal recessive primary microcephaly (ClinVar).

How common is ASPM p.Arg2732fs (c.8195_8196del) in the general population?

ASPM p.Arg2732fs (c.8195_8196del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ASPM p.Arg2732fs

c.8195_8196del · rs1558328295 · VCV2581671

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 18 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.23	GERP -2.3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,764 alleles

Overall 6.85e-05% 1/1,459,548 alleles · very rare

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: ASPM
Protein: p.Arg2732fs
Coding: c.8195_8196del
MANE Select: NM_018136
dbSNP: rs1558328295
Type: Deletion
Location: chr1:197101055 (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.Asn1533fs Pathogenic ★ same condition
ASPM p.Ser494fs 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-arg2732fs (accessed [today's date]).

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