Is ASPM p.Ile2341= (c.7023C>T) pathogenic?

ASPM p.Ile2341= (c.7023C>T) is classified Benign/Likely benign in ASPM (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Low-frequency (popmax 2.78%, afr); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Ile2341= (c.7023C>T)?

ASPM p.Ile2341= (c.7023C>T) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Ile2341= (c.7023C>T) in the general population?

ASPM p.Ile2341= (c.7023C>T) is low-frequency (popmax 2.78%, afr) (gnomAD).

ASPM p.Ile2341=

c.7023C>T · rs115891952 · VCV157861

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.78%, 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 -0.074	GERP -3.6, phastCons 0.17
Overall
CADD	5.405	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.78% African / African-American · 2,084/74,870 alleles

Filtering AF 2.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.64%

Overall 0.157% 2,530/1,612,702 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.78%	36
Middle Eastern	0.281%	356
Remaining individualsnot grpmax-eligible	0.255%	393
Admixed American	0.243%	412
European (non-Finnish)	0.00992%	10,079
South Asian	0.00879%	11,383

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.Ile2341=
Coding: c.7023C>T
MANE Select: NM_018136
dbSNP: rs115891952
Type: single nucleotide variant
Location: chr1:197102228 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2341: the iq 22 domain; the iq 23 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-ile2341 (accessed [today's date]).

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