Is ASPM p.Ser566Ter (c.1697C>A) pathogenic?

ASPM p.Ser566Ter (c.1697C>A) is classified Pathogenic in ASPM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-11). Absent from gnomAD v4.1; Associated with autosomal recessive primary microcephaly.

What condition is associated with ASPM p.Ser566Ter (c.1697C>A)?

ASPM p.Ser566Ter (c.1697C>A) is associated with autosomal recessive primary microcephaly (ClinVar).

How common is ASPM p.Ser566Ter (c.1697C>A) in the general population?

ASPM p.Ser566Ter (c.1697C>A) is absent from gnomAD v4.1 (gnomAD).

ASPM p.Ser566Ter

c.1697C>A · rs555866170 · VCV432552

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal recessive primary microcephaly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 28
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -3, phastCons 0.29
Overall
CADD	22.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASPM
Protein: p.Ser566Ter
Coding: c.1697C>A
MANE Select: NM_018136
dbSNP: rs555866170
Type: single nucleotide variant
Location: chr1:197142555 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 566: the 'disordered' region

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.Ser566Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ASPM p.Ser566= Likely benign ★ same residue
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
ASPM p.Glu1266Ter Pathogenic ★★ same condition
ASPM p.Tyr1665Ter Likely 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-ser566ter (accessed [today's date]).

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