Is ASPM p.Tyr2208fs (c.6623_6626del) pathogenic?

ASPM p.Tyr2208fs (c.66236626del) is classified Pathogenic in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Very rare (popmax 0.00133%, afr).

How common is ASPM p.Tyr2208fs (c.6623_6626del) in the general population?

ASPM p.Tyr2208fs (c.6623_6626del) is very rare (popmax 0.00133%, afr) (gnomAD).

ASPM p.Tyr2208fs

c.6623_6626del · rs1571599902 · VCV806300

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 18 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.066	GERP -3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,914 alleles

Overall 6.85e-05% 1/1,460,664 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.Tyr2208fs
Coding: c.6623_6626del
MANE Select: NM_018136
dbSNP: rs1571599902
Type: Deletion
Location: chr1:197102625 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2208: the iq 19 domain

Full ASPM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASPM p.Tyr2208Ter Pathogenic ★ same residue
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

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-tyr2208fs (accessed [today's date]).

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