Is ASPM p.Phe709fs (c.2126_2127del) pathogenic?

ASPM p.Phe709fs (c.21262127del) is classified Likely pathogenic in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-03). Associated with ASPM-related disorder.

What condition is associated with ASPM p.Phe709fs (c.2126_2127del)?

ASPM p.Phe709fs (c.2126_2127del) is associated with ASPM-related disorder (ClinVar).

ASPM p.Phe709fs

c.2126_2127del · VCV4925880

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ASPM-related disorder

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 0.35	GERP 0.61, phastCons 0.89

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

Variant & gene context

Gene: ASPM
Protein: p.Phe709fs
Coding: c.2126_2127del
MANE Select: NM_018136
Type: Deletion
Location: chr1:197135142 (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

ASPM-related disorder

Similar variants

ASPM p.Asp1285fs Pathogenic/Likely pathogenic ★★ same condition
ASPM p.Glu2731fs Pathogenic ★★ same condition
ASPM p.Glu511fs Pathogenic/Likely pathogenic ★★ same condition
ASPM p.Lys2712fs Pathogenic ★★ same condition
ASPM p.Leu334_Val335insTer Likely pathogenic ★ same condition
ASPM p.Asn533fs Pathogenic same condition
ASPM p.Arg1019Ter Pathogenic ★★ same condition
ASPM p.Asn653fs 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-phe709fs (accessed [today's date]).

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