Is ASPM p.Arg430Gly (c.1288A>G) pathogenic?

ASPM p.Arg430Gly (c.1288A>G) is classified Benign in ASPM (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.1067); Low-frequency (popmax 4.57%, afr); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Arg430Gly (c.1288A>G)?

ASPM p.Arg430Gly (c.1288A>G) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Arg430Gly (c.1288A>G) in the general population?

ASPM p.Arg430Gly (c.1288A>G) is low-frequency (popmax 4.57%, afr) (gnomAD).

What do computational predictors say about ASPM p.Arg430Gly (c.1288A>G)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

ASPM p.Arg430Gly

c.1288A>G · rs6428388 · VCV21553

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.57%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

microcephaly 5, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.074	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.68, phastCons 0.007
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	11.63	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.57% African / African-American · 3,432/75,028 alleles

Filtering AF 4.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.39%

Overall 0.26% 4,192/1,613,988 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.57%	22
Remaining individualsnot grpmax-eligible	0.389%	257
Admixed American	0.376%	266
Middle Eastern	0.231%	433
European (non-Finnish)	0.0226%	4,419
South Asian	0.00878%	11,385
Finnishnot grpmax-eligible	0.00312%	32,010

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.Arg430Gly
Coding: c.1288A>G
MANE Select: NM_018136
dbSNP: rs6428388
Type: single nucleotide variant
Location: chr1:197142964 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 430: the 'disordered' region; a UniProt-annotated variant site (in)

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.Arg430Ser Likely benign ★ 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-arg430gly (accessed [today's date]).

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