Is ASPM p.Lys698fs (c.2093del) pathogenic?

ASPM p.Lys698fs (c.2093del) is classified Pathogenic in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). Very rare (popmax 0.00017%, nfe).

How common is ASPM p.Lys698fs (c.2093del) in the general population?

ASPM p.Lys698fs (c.2093del) is very rare (popmax 0.00017%, nfe) (gnomAD).

ASPM p.Lys698fs

c.2093del · rs765613900 · VCV1373394

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)

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 5 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 0.18, phastCons 1

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) · 2/1,179,732 alleles

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

Overall 0.000137% 2/1,461,484 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.Lys698fs
Coding: c.2093del
MANE Select: NM_018136
dbSNP: rs765613900
Type: Deletion
Location: chr1:197135176 (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

Similar variants

ASPM p.Ala3113fs Pathogenic ★★ same type
ASPM p.Arg2005fs Pathogenic ★★ same type
ASPM p.Asn1095fs Likely pathogenic ★★ same type
ASPM p.Asn3136fs Likely pathogenic ★★ same type
ASPM p.Asn324fs Pathogenic/Likely pathogenic ★★ same type
ASPM p.Asn394fs Pathogenic ★★ same type
ASPM p.Asp1285fs Pathogenic/Likely pathogenic ★★ same type
ASPM p.Asp990fs Pathogenic ★★ same type

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-lys698fs (accessed [today's date]).

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