Is ASPM p.Lys920Arg (c.2759A>G) pathogenic?

ASPM p.Lys920Arg (c.2759A>G) is classified Uncertain significance in ASPM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-24). AlphaMissense: likely benign (0.144); Ultra-rare (popmax 0.0268%, eas); Associated with Inborn genetic diseases.

What condition is associated with ASPM p.Lys920Arg (c.2759A>G)?

ASPM p.Lys920Arg (c.2759A>G) is associated with Inborn genetic diseases, microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Lys920Arg (c.2759A>G) in the general population?

ASPM p.Lys920Arg (c.2759A>G) is ultra-rare (popmax 0.0268%, eas) (gnomAD).

What do computational predictors say about ASPM p.Lys920Arg (c.2759A>G)?

AlphaMissense predicts likely benign (score 0.144) — an in-silico prediction, not a clinical call.

ASPM p.Lys920Arg

c.2759A>G · rs372956877 · VCV1325961

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.144 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.144	likely benign
REVEL	0.502	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	32.0	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 0.0268% East Asian · 12/44,704 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00155% 25/1,612,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0268%	3,725
Remaining individualsnot grpmax-eligible	0.00961%	10,403
South Asian	0.0055%	18,171
European (non-Finnish)	0.00017%	589,261

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.Lys920Arg
Coding: c.2759A>G
MANE Select: NM_018136
dbSNP: rs372956877
Type: single nucleotide variant
Location: chr1:197129188 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 920: the calponin-homology (ch) 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microcephaly 5, primary, autosomal recessive

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-lys920arg (accessed [today's date]).

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