Is ASPM p.Ser311Arg (c.933C>G) pathogenic?

ASPM p.Ser311Arg (c.933C>G) is classified Conflicting classifications of pathogenicity in ASPM (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2025-10-06). AlphaMissense: likely benign (0.2899); Rare (popmax 0.508%, sas); Associated with Inborn genetic diseases.

What condition is associated with ASPM p.Ser311Arg (c.933C>G)?

ASPM p.Ser311Arg (c.933C>G) is associated with Inborn genetic diseases, microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Ser311Arg (c.933C>G) in the general population?

ASPM p.Ser311Arg (c.933C>G) is rare (popmax 0.508%, sas) (gnomAD).

What do computational predictors say about ASPM p.Ser311Arg (c.933C>G)?

AlphaMissense predicts likely benign (score 0.2899) — an in-silico prediction, not a clinical call.

ASPM p.Ser311Arg

c.933C>G · rs563858170 · VCV210363

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.2899 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.508%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2899	likely benign
REVEL	0.029	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 3.4	GERP -0.91, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,369 bp · p 0.063 · regional, not allelic
Overall
CADD	16.14	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 0.508% South Asian · 463/91,066 alleles

Filtering AF 0.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.455%

Overall 0.0418% 675/1,613,804 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.508%	197
Middle Eastern	0.281%	356
Remaining individualsnot grpmax-eligible	0.0768%	1,302
European (non-Finnish)	0.0122%	8,193
Admixed American	0.00333%	30,006
African / African-American	0.00133%	75,034

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.Ser311Arg
Coding: c.933C>G
MANE Select: NM_018136
dbSNP: rs563858170
Type: single nucleotide variant
Location: chr1:197143319 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 311: the 'sufficient for interaction with katna1:katnb1' 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

Also linked: microcephaly 5, primary, autosomal recessive

Similar variants

ASPM p.Ser311Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ser311arg (accessed [today's date]).

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