Is ASPM p.Asn560= (c.1680C>T) pathogenic?

ASPM p.Asn560= (c.1680C>T) is classified Likely benign in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). Very rare (popmax 0.00446%, eas).

How common is ASPM p.Asn560= (c.1680C>T) in the general population?

ASPM p.Asn560= (c.1680C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

ASPM p.Asn560=

c.1680C>T · rs751204699 · VCV2995126

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 -3.7
Overall
CADD	1.519	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00124% 20/1,613,614 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,821
East Asiangrpmax	0.00446%	22,440
Admixed American	0.00333%	29,996
African / African-American	0.00267%	37,439
South Asian	0.0011%	91,080
European (non-Finnish)	0.000848%	117,972

Remaining individuals 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.Asn560=
Coding: c.1680C>T
MANE Select: NM_018136
dbSNP: rs751204699
Type: single nucleotide variant
Location: chr1:197142572 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 560: the 'disordered' region

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

Similar variants

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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-asn560 (accessed [today's date]).

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