Is ASPM p.Val2172fs (c.6513dup) pathogenic?

ASPM p.Val2172fs (c.6513dup) is classified Pathogenic in ASPM (ClinVar, Single submitter, 1 submitter). Ultra-rare (gnomAD MAF 7.141e-07); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Val2172fs (c.6513dup)?

ASPM p.Val2172fs (c.6513dup) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Val2172fs (c.6513dup) in the general population?

ASPM p.Val2172fs (c.6513dup) is ultra-rare (gnomAD MAF 7.141e-07) (gnomAD).

ASPM p.Val2172fs

c.6513dup · rs1571600045 · VCV694007

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.141e-07)

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 18 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.86	GERP -3.7

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

Population frequency

dbSNP / gnomAD

Global frequency 7.14e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: ASPM
Protein: p.Val2172fs
Coding: c.6513dup
MANE Select: NM_018136
dbSNP: rs1571600045
Type: Duplication
Location: chr1:197102737 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2172: the iq 18 domain

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.Val2172Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
ASPM p.Arg2184fs Pathogenic/Likely pathogenic ★★ same condition
ASPM p.Gln2377fs Pathogenic/Likely pathogenic ★★ same condition
ASPM p.Gln2620fs Pathogenic ★★ same condition
ASPM p.Ile2445fs Pathogenic ★★ same condition
ASPM p.Glu1480dup Uncertain significance ★★ same condition
ASPM c.3742-3dup Benign/Likely benign ★★ same condition
ASPM p.Arg980fs 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-val2172fs (accessed [today's date]).

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