Is ASPM p.Arg3198Ser (c.9592C>A) pathogenic?

ASPM p.Arg3198Ser (c.9592C>A) is classified Uncertain significance in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: ambiguous (0.3489); Very rare (popmax 0.00549%, sas); Associated with Inborn genetic diseases.

What condition is associated with ASPM p.Arg3198Ser (c.9592C>A)?

ASPM p.Arg3198Ser (c.9592C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ASPM p.Arg3198Ser (c.9592C>A) in the general population?

ASPM p.Arg3198Ser (c.9592C>A) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about ASPM p.Arg3198Ser (c.9592C>A)?

AlphaMissense predicts ambiguous (score 0.3489) — an in-silico prediction, not a clinical call.

ASPM p.Arg3198Ser

c.9592C>A · VCV4156208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3489 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3489	ambiguous
REVEL	0.147	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.051	GERP -1
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	3.513	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 0.00549% South Asian · 5/91,040 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000434% 7/1,612,984 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,208
East Asian	0.00223%	44,820
Remaining individualsnot grpmax-eligible	0.0016%	62,438

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.Arg3198Ser
Coding: c.9592C>A
MANE Select: NM_018136
Type: single nucleotide variant
Location: chr1:197090894 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3198: the iq 38 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.Arg3198His Uncertain significance ★★ ⚠ same residue
ASPM p.Arg3198Cys 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-arg3198ser (accessed [today's date]).

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