Is ASPM p.Arg573Trp (c.1717C>T) pathogenic?

ASPM p.Arg573Trp (c.1717C>T) is classified Conflicting classifications of pathogenicity in ASPM (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.122); Low-frequency (popmax 1.07%, mid); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Arg573Trp (c.1717C>T)?

ASPM p.Arg573Trp (c.1717C>T) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Arg573Trp (c.1717C>T) in the general population?

ASPM p.Arg573Trp (c.1717C>T) is low-frequency (popmax 1.07%, mid) (gnomAD).

What do computational predictors say about ASPM p.Arg573Trp (c.1717C>T)?

AlphaMissense predicts likely benign (score 0.122) — an in-silico prediction, not a clinical call.

ASPM p.Arg573Trp

c.1717C>T · rs144049904 · VCV157784

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.122 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

microcephaly 5, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.122	likely benign
REVEL	0.115	moderately 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 0.84	GERP 1.1
Regional constraint	o/e 1.01	unconstrained · MANE · 59 kb · p 0.59 · regional, not allelic
Overall
CADD	20.7	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 1.07% Middle Eastern · 65/6,062 alleles

Filtering AF 0.863% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.787%

Overall 0.255% 4,121/1,613,904 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.07%	93
Ashkenazi Jewishnot grpmax-eligible	0.524%	191
Admixed American	0.412%	243
Remaining individualsnot grpmax-eligible	0.336%	298
European (non-Finnish)	0.285%	351
African / African-American	0.0387%	2,586
South Asian	0.034%	2,938
Finnishnot grpmax-eligible	0.0266%	3,764
East Asian	0.00223%	44,866

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.Arg573Trp
Coding: c.1717C>T
MANE Select: NM_018136
dbSNP: rs144049904
Type: single nucleotide variant
Location: chr1:197142535 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 573: the 'disordered' region

Full ASPM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly 5, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASPM c.2419+2T>C Pathogenic/Likely pathogenic ★★ same condition
ASPM c.2488-1G>C Pathogenic/Likely pathogenic ★★ same condition
ASPM c.2936+5G>A Likely pathogenic ★★ same condition
ASPM c.3082+1G>C Pathogenic/Likely pathogenic ★★ same condition
ASPM c.9084+5G>A Likely pathogenic ★★ same condition
ASPM p.Arg1019Ter Pathogenic ★★ same condition
ASPM p.Arg1271Ter Pathogenic ★★ same condition
ASPM p.Arg1538Ter Pathogenic ★★ 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-arg573trp (accessed [today's date]).

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