Is ASPM p.Ala1160= (c.3480T>A) pathogenic?

ASPM p.Ala1160= (c.3480T>A) is classified Uncertain significance in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). Very rare (popmax 0.00661%, nfe); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Ala1160= (c.3480T>A)?

ASPM p.Ala1160= (c.3480T>A) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Ala1160= (c.3480T>A) in the general population?

ASPM p.Ala1160= (c.3480T>A) is very rare (popmax 0.00661%, nfe) (gnomAD).

ASPM p.Ala1160=

c.3480T>A · rs373180437 · VCV876901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00661%, nfe)

Conditions

microcephaly 5, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP -3.7
Overall
CADD	4.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00661% European (non-Finnish) · 78/1,179,748 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00527% 85/1,613,546 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00661%	15,125
Remaining individualsnot grpmax-eligible	0.0064%	15,615
African / African-American	0.004%	24,975

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.Ala1160=
Coding: c.3480T>A
MANE Select: NM_018136
dbSNP: rs373180437
Type: single nucleotide variant
Location: chr1:197122506 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1160: the calponin-homology (ch) 2 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 c.2419+2T>C Pathogenic/Likely pathogenic ★★ same condition
ASPM c.2488-1G>C Pathogenic/Likely pathogenic ★★ same condition
ASPM c.2936+5G>A Likely pathogenic ★★ same condition
ASPM c.3082+1G>C Pathogenic/Likely pathogenic ★★ same condition
ASPM c.9084+5G>A Likely pathogenic ★★ same condition
ASPM p.Arg1019Ter Pathogenic ★★ same condition
ASPM p.Arg1271Ter Pathogenic ★★ same condition
ASPM p.Arg1538Ter 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-ala1160 (accessed [today's date]).

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