Is ASPM p.Ala2393= (c.7179T>A) pathogenic?

ASPM p.Ala2393= (c.7179T>A) is classified Conflicting classifications of pathogenicity in ASPM (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-17). Rare (popmax 0.348%, eas); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Ala2393= (c.7179T>A)?

ASPM p.Ala2393= (c.7179T>A) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Ala2393= (c.7179T>A) in the general population?

ASPM p.Ala2393= (c.7179T>A) is rare (popmax 0.348%, eas) (gnomAD).

ASPM p.Ala2393=

c.7179T>A · rs117668001 · VCV738216

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.348%, eas)

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 -0.09	GERP 0.43
Overall
CADD	8.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.348% East Asian · 156/44,830 alleles

Filtering AF 0.303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.286%

Overall 0.0127% 205/1,613,038 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.348%	287
South Asian	0.0384%	2,602
Remaining individualsnot grpmax-eligible	0.0208%	4,805
Admixed American	0.00167%	59,872

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.Ala2393=
Coding: c.7179T>A
MANE Select: NM_018136
dbSNP: rs117668001
Type: single nucleotide variant
Location: chr1:197102072 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2393: the iq 24 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-ala2393 (accessed [today's date]).

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