Is ASPM p.Arg3103fs (c.9309_9310del) pathogenic?

ASPM p.Arg3103fs (c.93099310del) is classified Pathogenic in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). Very rare (popmax 0.00017%, nfe); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Arg3103fs (c.9309_9310del)?

ASPM p.Arg3103fs (c.9309_9310del) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Arg3103fs (c.9309_9310del) in the general population?

ASPM p.Arg3103fs (c.9309_9310del) is very rare (popmax 0.00017%, nfe) (gnomAD).

ASPM p.Arg3103fs

c.9309_9310del · rs587783289 · VCV157908

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 22 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -0.43, phastCons 0.075

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,478 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,459,692 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.Arg3103fs
Coding: c.9309_9310del
MANE Select: NM_018136
dbSNP: rs587783289
Type: Microsatellite
Location: chr1:197092041 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3103: the iq 37 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.Arg3103Ser Uncertain significance ★ ⚠ same residue
ASPM p.Arg1315fs Pathogenic ★★ same condition
ASPM p.Arg1416_Tyr1417insTer Pathogenic ★★ same condition
ASPM p.Arg1576fs Pathogenic/Likely pathogenic ★★ same condition
ASPM p.Arg2229fs Pathogenic ★★ same condition
ASPM p.Asn653fs Pathogenic ★★ same condition
ASPM p.Gln2836fs Pathogenic/Likely pathogenic ★★ same condition
ASPM p.Glu385fs 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-arg3103fs (accessed [today's date]).

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