Is ASPM p.Ile2040Lys (c.6119T>A) pathogenic?

ASPM p.Ile2040Lys (c.6119T>A) is classified Uncertain significance in ASPM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-21). AlphaMissense: likely benign (0.2446); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ASPM p.Ile2040Lys (c.6119T>A)?

ASPM p.Ile2040Lys (c.6119T>A) is associated with Inborn genetic diseases (ClinVar).

How common is ASPM p.Ile2040Lys (c.6119T>A) in the general population?

ASPM p.Ile2040Lys (c.6119T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPM p.Ile2040Lys (c.6119T>A)?

AlphaMissense predicts likely benign (score 0.2446) — an in-silico prediction, not a clinical call.

ASPM p.Ile2040Lys

c.6119T>A · rs2527298275 · VCV2041300

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2446 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2446	likely benign
REVEL	0.336	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.28, phastCons 0.88
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	22.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASPM
Protein: p.Ile2040Lys
Coding: c.6119T>A
MANE Select: NM_018136
dbSNP: rs2527298275
Type: single nucleotide variant
Location: chr1:197103132 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2040: the iq 14 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

Similar variants

ASPM p.Arg3304Ter Pathogenic ★★ same condition
ASPM p.Arg3390Ter Pathogenic ★★ same condition
ASPM p.Gln3060Ter Pathogenic ★★ same condition
ASPM p.Gln3321Ter Pathogenic ★★ same condition
ASPM p.Trp989Ter Pathogenic ★★ same condition
ASPM p.Ala1125Val Uncertain significance ★★ ⚠ same condition
ASPM p.Ala1319Ser Uncertain significance ★★ ⚠ same condition
ASPM p.Ala1468Thr Uncertain significance ★★ 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-ile2040lys (accessed [today's date]).

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