Is ASPM p.Val844= (c.2532C>T) pathogenic?

ASPM p.Val844= (c.2532C>T) is classified Conflicting classifications of pathogenicity in ASPM (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.0144%, nfe); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Val844= (c.2532C>T)?

ASPM p.Val844= (c.2532C>T) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Val844= (c.2532C>T) in the general population?

ASPM p.Val844= (c.2532C>T) is ultra-rare (popmax 0.0144%, nfe) (gnomAD).

ASPM p.Val844=

c.2532C>T · rs141716537 · VCV294643

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 0.0144%, nfe)

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 1.8	GERP 1.6, phastCons 1
Overall
CADD	9.887	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0144% European (non-Finnish) · 170/1,179,916 alleles

Filtering AF 0.0126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.0108% 175/1,613,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0144%	6,941
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Admixed American	0.00167%	60,006
African / African-American	0.00133%	74,924

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.Val844=
Coding: c.2532C>T
MANE Select: NM_018136
dbSNP: rs141716537
Type: single nucleotide variant
Location: chr1:197130012 (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-val844 (accessed [today's date]).

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