Is ASPM p.Arg793Trp (c.2377C>T) pathogenic?

ASPM p.Arg793Trp (c.2377C>T) is classified Uncertain significance in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.2281); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with ASPM p.Arg793Trp (c.2377C>T)?

ASPM p.Arg793Trp (c.2377C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ASPM p.Arg793Trp (c.2377C>T) in the general population?

ASPM p.Arg793Trp (c.2377C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ASPM p.Arg793Trp (c.2377C>T)?

AlphaMissense predicts likely benign (score 0.2281) — an in-silico prediction, not a clinical call.

ASPM p.Arg793Trp

c.2377C>T · VCV3318742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2281 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2281	likely benign
REVEL	0.365	indeterminate
Splicing
SpliceAI	Δ0.32	donor loss, 42 bp away · masked 0 · deltas
Pangolin	Δ0.22	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.5	GERP 0.061, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	24.3	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 0.00334% Admixed American · 2/59,960 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00118% 19/1,613,646 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,980
South Asian	0.00329%	30,350
Remaining individualsnot grpmax-eligible	0.0032%	31,238
Finnishnot grpmax-eligible	0.00312%	32,002
European (non-Finnish)	0.000848%	117,985

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.Arg793Trp
Coding: c.2377C>T
MANE Select: NM_018136
Type: single nucleotide variant
Location: chr1:197133392 (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.Arg793Gln Uncertain significance ★ ⚠ same residue
ASPM p.Arg793= Likely benign ★ 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-arg793trp (accessed [today's date]).

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