Is ASPM p.Arg2682Gln (c.8045G>A) pathogenic?

ASPM p.Arg2682Gln (c.8045G>A) is classified Uncertain significance in ASPM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-11). AlphaMissense: likely benign (0.0928); Ultra-rare (popmax 0.0218%, amr); Associated with Inborn genetic diseases.

What condition is associated with ASPM p.Arg2682Gln (c.8045G>A)?

ASPM p.Arg2682Gln (c.8045G>A) is associated with Inborn genetic diseases, microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Arg2682Gln (c.8045G>A) in the general population?

ASPM p.Arg2682Gln (c.8045G>A) is ultra-rare (popmax 0.0218%, amr) (gnomAD).

What do computational predictors say about ASPM p.Arg2682Gln (c.8045G>A)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

ASPM p.Arg2682Gln

c.8045G>A · rs777169562 · VCV1511123

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0218%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.267	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -3.5
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	15.29	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0218% Admixed American · 13/59,712 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.00664% 107/1,612,146 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0218%	4,593
Remaining individualsnot grpmax-eligible	0.00962%	10,394
European (non-Finnish)	0.00729%	13,710
African / African-American	0.00267%	37,386

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.Arg2682Gln
Coding: c.8045G>A
MANE Select: NM_018136
dbSNP: rs777169562
Type: single nucleotide variant
Location: chr1:197101206 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2682: the iq 29 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 p.Arg2682Ter Likely pathogenic ★ same residue
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

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-arg2682gln (accessed [today's date]).

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