Is ASPM p.Val2535= (c.7605G>A) pathogenic?

ASPM p.Val2535= (c.7605G>A) is classified Benign in ASPM (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-03). Common (popmax 68.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Val2535= (c.7605G>A)?

ASPM p.Val2535= (c.7605G>A) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

ASPM p.Val2535=

Q: How common is ASPM p.Val2535= (c.7605G>A) in the general population?

ASPM p.Val2535= (c.7605G>A) is common (popmax 68.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7605G>A · rs10922162 · VCV21603

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 68.5%, eas) — too common for a highly-penetrant pathogenic allele

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 -0.47	GERP -0.7
Overall
CADD	0.639	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 68.5% East Asian · 30,674/44,762 alleles

Filtering AF 67.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 67.6%

Overall 19.1% 307,490/1,611,328 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	68.5%	1
Admixed American	42.4%	2
South Asian	27.8%	4
Finnishnot grpmax-eligible	24.2%	4
Remaining individualsnot grpmax-eligible	20.8%	5
Ashkenazi Jewishnot grpmax-eligible	18.1%	6
European (non-Finnish)	16%	6
Middle Eastern	13.1%	8
Amishnot grpmax-eligible	6.47%	15
African / African-American	3.82%	26

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.Val2535=
Coding: c.7605G>A
MANE Select: NM_018136
dbSNP: rs10922162
Type: single nucleotide variant
Location: chr1:197101646 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2535: the iq 27 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-val2535 (accessed [today's date]).

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