Is ASPM p.Gln395= (c.1185A>G) pathogenic?

ASPM p.Gln395= (c.1185A>G) is classified Conflicting classifications of pathogenicity in ASPM (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-01). Ultra-rare (popmax 0.087%, eas); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Gln395= (c.1185A>G)?

ASPM p.Gln395= (c.1185A>G) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Gln395= (c.1185A>G) in the general population?

ASPM p.Gln395= (c.1185A>G) is ultra-rare (popmax 0.087%, eas) (gnomAD).

ASPM p.Gln395=

c.1185A>G · rs183395856 · VCV294655

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.087%, 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 -4.7	GERP -2.3
Overall
CADD	0.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.087% East Asian · 39/44,848 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00564% 91/1,613,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.087%	1,150
Middle Eastern	0.0165%	6,054
Admixed American	0.015%	6,667
Remaining individualsnot grpmax-eligible	0.0096%	10,412
South Asian	0.00879%	11,381
African / African-American	0.00667%	14,998
European (non-Finnish)	0.00195%	51,266

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.Gln395=
Coding: c.1185A>G
MANE Select: NM_018136
dbSNP: rs183395856
Type: single nucleotide variant
Location: chr1:197143067 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 395: the 'sufficient for interaction with katna1:katnb1' region

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.Gln395Arg Uncertain significance ★★ ⚠ same residue
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

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-gln395 (accessed [today's date]).

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