Is ASPM p.Ala3002= (c.9006A>G) pathogenic?

ASPM p.Ala3002= (c.9006A>G) is classified Likely benign in ASPM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-10). Ultra-rare (popmax 0.0871%, afr); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Ala3002= (c.9006A>G)?

ASPM p.Ala3002= (c.9006A>G) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Ala3002= (c.9006A>G) in the general population?

ASPM p.Ala3002= (c.9006A>G) is ultra-rare (popmax 0.0871%, afr) (gnomAD).

ASPM p.Ala3002=

c.9006A>G · rs143760252 · VCV387515

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0871%, afr)

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 -0.67	GERP -1.1, phastCons 0.057
Overall
CADD	6.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0871% African / African-American · 65/74,644 alleles

Filtering AF 0.0701% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0639%

Overall 0.00523% 84/1,605,680 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0871%	1,148
Remaining individualsnot grpmax-eligible	0.00967%	10,346
Admixed American	0.00505%	19,813
European (non-Finnish)	0.000851%	117,471

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.Ala3002=
Coding: c.9006A>G
MANE Select: NM_018136
dbSNP: rs143760252
Type: single nucleotide variant
Location: chr1:197094162 (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

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-ala3002 (accessed [today's date]).

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