Is ASPM p.Ile1083Val (c.3247A>G) pathogenic?

ASPM p.Ile1083Val (c.3247A>G) is classified Conflicting classifications of pathogenicity in ASPM (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-24). AlphaMissense: likely benign (0.0671); Very rare (popmax 0.00224%, eas); Associated with Inborn genetic diseases.

What condition is associated with ASPM p.Ile1083Val (c.3247A>G)?

ASPM p.Ile1083Val (c.3247A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ASPM p.Ile1083Val (c.3247A>G) in the general population?

ASPM p.Ile1083Val (c.3247A>G) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about ASPM p.Ile1083Val (c.3247A>G)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

ASPM p.Ile1083Val

c.3247A>G · rs772918163 · VCV379166

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.015	strongly 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 -3.9	GERP -3
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	0.015	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 0.00224% East Asian · 1/44,672 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000343% 5/1,456,234 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,672
European (non-Finnish)	0.00034%	293,859

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.Ile1083Val
Coding: c.3247A>G
MANE Select: NM_018136
dbSNP: rs772918163
Type: single nucleotide variant
Location: chr1:197124253 (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-ile1083val (accessed [today's date]).

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