Is ASPM p.Ala28Pro (c.82G>C) pathogenic?

ASPM p.Ala28Pro (c.82G>C) is classified Uncertain significance in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely benign (0.1128); Very rare (popmax 0.00834%, amr); Associated with Inborn genetic diseases.

What condition is associated with ASPM p.Ala28Pro (c.82G>C)?

ASPM p.Ala28Pro (c.82G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ASPM p.Ala28Pro (c.82G>C) in the general population?

ASPM p.Ala28Pro (c.82G>C) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about ASPM p.Ala28Pro (c.82G>C)?

AlphaMissense predicts likely benign (score 0.1128) — an in-silico prediction, not a clinical call.

ASPM p.Ala28Pro

c.82G>C · rs912338232 · VCV2265279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1128 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1128	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -0.57
Regional constraint	o/e 1.09	unconstrained · MANE · 3,369 bp · p 0.063 · regional, not allelic
Overall
CADD	12.41	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,966 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,610,412 alleles · very rare exomes 5/1,458,414 · genomes 0/151,998 · joint denominator

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.Ala28Pro
Coding: c.82G>C
MANE Select: NM_018136
dbSNP: rs912338232
Type: single nucleotide variant
Location: chr1:197146356 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 28: the 'disordered' region

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.Ala28Gly Uncertain significance ★ ⚠ same residue
ASPM p.Ala28Val Uncertain significance ★ ⚠ same residue
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

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-ala28pro (accessed [today's date]).

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