Is ASPM p.Ser935= (c.2805T>C) pathogenic?

ASPM p.Ser935= (c.2805T>C) is classified Benign in ASPM (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-05-01). Low-frequency (popmax 1.34%, nfe); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Ser935= (c.2805T>C)?

ASPM p.Ser935= (c.2805T>C) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Ser935= (c.2805T>C) in the general population?

ASPM p.Ser935= (c.2805T>C) is low-frequency (popmax 1.34%, nfe) (gnomAD).

ASPM p.Ser935=

c.2805T>C · rs113161395 · VCV21567

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.34%, 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 -1.7	GERP -1.1
Overall
CADD	4.291	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.34% European (non-Finnish) · 15,820/1,179,746 alleles

Filtering AF 1.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.32%

Overall 1.19% 19,280/1,613,798 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.56%	28
European (non-Finnish)grpmax	1.34%	75
Remaining individualsnot grpmax-eligible	0.986%	101
Ashkenazi Jewishnot grpmax-eligible	0.426%	235
Admixed American	0.238%	420
African / African-American	0.192%	521
South Asian	0.156%	641
Middle Eastern	0.099%	1,010
East Asian	0.00446%	22,430

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser935=
Coding: c.2805T>C
MANE Select: NM_018136
dbSNP: rs113161395
Type: single nucleotide variant
Location: chr1:197128621 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 935: the calponin-homology (ch) 1 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-ser935 (accessed [today's date]).

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