Is ASPM p.Lys103= (c.309A>G) pathogenic?

ASPM p.Lys103= (c.309A>G) is classified Likely benign in ASPM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-23). Ultra-rare (popmax 0.0498%, mid); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Lys103= (c.309A>G)?

ASPM p.Lys103= (c.309A>G) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Lys103= (c.309A>G) in the general population?

ASPM p.Lys103= (c.309A>G) is ultra-rare (popmax 0.0498%, mid) (gnomAD).

ASPM p.Lys103=

c.309A>G · rs587783229 · VCV157802

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0498%, mid)

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 2.4	GERP 0.3, phastCons 1
Overall
CADD	10.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0498% Middle Eastern · 3/6,028 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00125% 20/1,603,706 alleles · ultra-rare exomes 18/1,451,522 · genomes 2/152,184 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0498%	2,009
Admixed American	0.00667%	14,994
Remaining individualsnot grpmax-eligible	0.00644%	15,532
South Asian	0.0022%	45,382
European (non-Finnish)	0.000598%	167,293

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.Lys103=
Coding: c.309A>G
MANE Select: NM_018136
dbSNP: rs587783229
Type: single nucleotide variant
Location: chr1:197144089 (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-lys103 (accessed [today's date]).

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