Is NDE1 p.Arg44Ter (c.130C>T) pathogenic?

NDE1 p.Arg44Ter (c.130C>T) is classified Conflicting classifications of pathogenicity in NDE1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-08). Very rare (popmax 0.00223%, eas); Associated with NDE1-related microhydranencephaly.

What condition is associated with NDE1 p.Arg44Ter (c.130C>T)?

NDE1 p.Arg44Ter (c.130C>T) is associated with NDE1-related microhydranencephaly, lissencephaly 4 (ClinVar).

How common is NDE1 p.Arg44Ter (c.130C>T) in the general population?

NDE1 p.Arg44Ter (c.130C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

NDE1 p.Arg44Ter

c.130C>T · rs747020521 · VCV1120133

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

NDE1-related microhydranencephaly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 9
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP -0.99, phastCons 1
Overall
CADD	39.0	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 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,613,888 alleles · very rare exomes 4/1,461,886 · genomes 3/152,002 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Finnishnot grpmax-eligible	0.00156%	63,988
European (non-Finnish)	0.000424%	236,004

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: NDE1
Protein: p.Arg44Ter
Coding: c.130C>T
MANE Select: NM_017668
dbSNP: rs747020521
Type: single nucleotide variant
Location: chr16:15667332 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.40 · 1 PDB
Residue 44: the 'self-association' region

Full NDE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: lissencephaly 4

Similar variants

NDE1 p.Arg220Ter Pathogenic/Likely pathogenic ★★ same condition
NDE1 p.Arg37Ter Pathogenic ★★ same condition
MYH11 p.Glu1344Val Uncertain significance ★★ ⚠ same condition
NDE1 p.Ala101Val Uncertain significance ★★ ⚠ same condition
NDE1 p.Ala208Val Uncertain significance ★★ ⚠ same condition
NDE1 p.Arg234His Uncertain significance ★★ ⚠ same condition
NDE1 p.Arg275Trp Uncertain significance ★★ ⚠ same condition
NDE1 p.Arg62Gly 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/nde1-p-arg44ter (accessed [today's date]).

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