Is NDE1 p.Ser4= (c.12C>T) pathogenic?

NDE1 p.Ser4= (c.12C>T) is classified Conflicting classifications of pathogenicity in NDE1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-12-31). Ultra-rare (popmax 0.0167%, amr); Associated with lissencephaly 4.

What condition is associated with NDE1 p.Ser4= (c.12C>T)?

NDE1 p.Ser4= (c.12C>T) is associated with lissencephaly 4 (ClinVar).

How common is NDE1 p.Ser4= (c.12C>T) in the general population?

NDE1 p.Ser4= (c.12C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

NDE1 p.Ser4=

c.12C>T · rs572790932 · VCV318045

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Conditions

lissencephaly 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -4
Overall
CADD	0.153	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/59,960 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.00254% 41/1,612,798 alleles · ultra-rare exomes 34/1,460,778 · genomes 7/152,020 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,996
South Asian	0.00769%	13,006
European (non-Finnish)	0.00178%	56,142
Remaining individualsnot grpmax-eligible	0.0016%	62,480
Finnishnot grpmax-eligible	0.00156%	63,964
African / African-American	0.00133%	74,936

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.Ser4=
Coding: c.12C>T
MANE Select: NM_017668
dbSNP: rs572790932
Type: single nucleotide variant
Location: chr16:15664790 (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 4: the 'self-association' region

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

Disease context

lissencephaly 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser4 (accessed [today's date]).

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