Is ASPM p.Val1012Phe (c.3034G>T) pathogenic?

ASPM p.Val1012Phe (c.3034G>T) is classified Uncertain significance in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: ambiguous (0.4146); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ASPM p.Val1012Phe (c.3034G>T)?

ASPM p.Val1012Phe (c.3034G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ASPM p.Val1012Phe (c.3034G>T) in the general population?

ASPM p.Val1012Phe (c.3034G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ASPM p.Val1012Phe (c.3034G>T)?

AlphaMissense predicts ambiguous (score 0.4146) — an in-silico prediction, not a clinical call.

ASPM p.Val1012Phe

c.3034G>T · rs1468614422 · VCV3130469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4146	ambiguous
REVEL	0.356	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,970 alleles

Overall 0.000137% 2/1,461,774 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,012
European (non-Finnish)grpmax	8.47e-05%	1,179,970

Finnish 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.Val1012Phe
Coding: c.3034G>T
MANE Select: NM_018136
dbSNP: rs1468614422
Type: single nucleotide variant
Location: chr1:197125094 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1012: the calponin-homology (ch) 1 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-val1012phe (accessed [today's date]).

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