Is ASPM p.Glu608fs (c.1823_1824del) pathogenic?

ASPM p.Glu608fs (c.18231824del) is classified Pathogenic in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). Very rare (popmax 0.00134%, afr); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Glu608fs (c.1823_1824del)?

ASPM p.Glu608fs (c.1823_1824del) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Glu608fs (c.1823_1824del) in the general population?

ASPM p.Glu608fs (c.1823_1824del) is very rare (popmax 0.00134%, afr) (gnomAD).

ASPM p.Glu608fs

c.1823_1824del · rs779765020 · VCV1710439

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 3 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.39	GERP -3.7
Overall
CADD	22.0	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

Grpmax group 0.00134% African / African-American · 1/74,898 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,613,786 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,898
European (non-Finnish)	0.000593%	168,547

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.Glu608fs
Coding: c.1823_1824del
MANE Select: NM_018136
dbSNP: rs779765020
Type: Microsatellite
Location: chr1:197142428 (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

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

Similar variants

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
ASPM p.Ile2113fs 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-glu608fs (accessed [today's date]).

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