Is ASPM p.Arg2518= (c.7554A>G) pathogenic?

ASPM p.Arg2518= (c.7554A>G) is classified Conflicting classifications of pathogenicity in ASPM (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-07). Low-frequency (popmax 1.18%, afr); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Arg2518= (c.7554A>G)?

ASPM p.Arg2518= (c.7554A>G) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Arg2518= (c.7554A>G) in the general population?

ASPM p.Arg2518= (c.7554A>G) is low-frequency (popmax 1.18%, afr) (gnomAD).

ASPM p.Arg2518=

c.7554A>G · rs140248383 · VCV157871

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.18%, 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 1	GERP -0.92, phastCons 0.81
Overall
CADD	7.501	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.18% African / African-American · 886/74,908 alleles

Filtering AF 1.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.09%

Overall 0.0659% 1,062/1,612,294 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.18%	85
Admixed American	0.132%	757
Middle Eastern	0.0991%	1,009
Remaining individualsnot grpmax-eligible	0.0625%	1,601
European (non-Finnish)	0.00433%	23,120
South Asian	0.0011%	91,056

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.Arg2518=
Coding: c.7554A>G
MANE Select: NM_018136
dbSNP: rs140248383
Type: single nucleotide variant
Location: chr1:197101697 (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 p.Arg2518Lys 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-arg2518 (accessed [today's date]).

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