Is ASPM p.Arg3107Ter (c.9319C>T) pathogenic?

ASPM p.Arg3107Ter (c.9319C>T) is classified Pathogenic in ASPM (ClinVar, Single submitter, 2 submitters; last evaluated 2022-01-05). Very rare (popmax 0.0011%, sas); Associated with microcephaly 5, primary, autosomal recessive.

What condition is associated with ASPM p.Arg3107Ter (c.9319C>T)?

ASPM p.Arg3107Ter (c.9319C>T) is associated with microcephaly 5, primary, autosomal recessive (ClinVar).

How common is ASPM p.Arg3107Ter (c.9319C>T) in the general population?

ASPM p.Arg3107Ter (c.9319C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

ASPM p.Arg3107Ter

c.9319C>T · rs199422187 · VCV21623

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

microcephaly 5, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 22 of 28
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Pangolin	Δ0.49	loss · gain 0.10 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 0.63	GERP 0.38
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,012 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000343% 5/1,459,764 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,012
European (non-Finnish)	0.000339%	294,631

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.Arg3107Ter
Coding: c.9319C>T
MANE Select: NM_018136
dbSNP: rs199422187
Type: single nucleotide variant
Location: chr1:197092032 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3107: the iq 37 domain

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 p.Arg3107Gln Uncertain significance ★ ⚠ 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-arg3107ter (accessed [today's date]).

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