Is ASPM p.Gln1663Glu (c.4987C>G) pathogenic?

ASPM p.Gln1663Glu (c.4987C>G) is classified Uncertain significance in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-30). AlphaMissense: likely benign (0.2406); Very rare (popmax 0.00223%, eas).

How common is ASPM p.Gln1663Glu (c.4987C>G) in the general population?

ASPM p.Gln1663Glu (c.4987C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ASPM p.Gln1663Glu (c.4987C>G)?

AlphaMissense predicts likely benign (score 0.2406) — an in-silico prediction, not a clinical call.

ASPM p.Gln1663Glu

c.4987C>G · rs2527303355 · VCV2814342

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2406 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.2406	likely benign
REVEL	0.673	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,792 alleles

Overall 6.85e-05% 1/1,460,914 alleles · very rare

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.Gln1663Glu
Coding: c.4987C>G
MANE Select: NM_018136
dbSNP: rs2527303355
Type: single nucleotide variant
Location: chr1:197104264 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1663: the iq 5 domain

Full ASPM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASPM c.2419+2T>C Pathogenic/Likely pathogenic ★★ same type
ASPM c.2488-1G>C Pathogenic/Likely pathogenic ★★ same type
ASPM c.2936+5G>A Likely pathogenic ★★ same type
ASPM c.3082+1G>C Pathogenic/Likely pathogenic ★★ same type
ASPM c.9084+5G>A Likely pathogenic ★★ same type
ASPM p.Arg1019Ter Pathogenic ★★ same type
ASPM p.Arg1271Ter Pathogenic ★★ same type
ASPM p.Arg1392Ter Pathogenic ★★ same type

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-gln1663glu (accessed [today's date]).

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