Is ASPM p.Asp540Val (c.1619A>T) pathogenic?

ASPM p.Asp540Val (c.1619A>T) is classified Uncertain significance in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.0692); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ASPM p.Asp540Val (c.1619A>T)?

ASPM p.Asp540Val (c.1619A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ASPM p.Asp540Val (c.1619A>T) in the general population?

ASPM p.Asp540Val (c.1619A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPM p.Asp540Val (c.1619A>T)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

ASPM p.Asp540Val

c.1619A>T · VCV4156229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.045	moderately 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 -1.5	GERP -3.7
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	2.421	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

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.Asp540Val
Coding: c.1619A>T
MANE Select: NM_018136
Type: single nucleotide variant
Location: chr1:197142633 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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-asp540val (accessed [today's date]).

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