Is NDE1 p.Phe39Ser (c.116T>C) pathogenic?

NDE1 p.Phe39Ser (c.116T>C) is classified Uncertain significance in NDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). AlphaMissense: likely pathogenic (0.9986); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NDE1 p.Phe39Ser (c.116T>C)?

NDE1 p.Phe39Ser (c.116T>C) is associated with Inborn genetic diseases (ClinVar).

How common is NDE1 p.Phe39Ser (c.116T>C) in the general population?

NDE1 p.Phe39Ser (c.116T>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about NDE1 p.Phe39Ser (c.116T>C)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

NDE1 p.Phe39Ser

c.116T>C · VCV3403721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic · top 2% in NDE1
REVEL	0.586	indeterminate
SaProt	LLR -15.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 2.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 59 kb · p 0.74 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,020 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,964 alleles · very rare exomes 1/1,461,886 · genomes 1/152,078 · joint denominator

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.Phe39Ser
Coding: c.116T>C
MANE Select: NM_017668
Type: single nucleotide variant
Location: chr16:15667318 (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 39: the 'self-association' region

Full NDE1 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

Similar variants

NDE1 p.Phe39= Uncertain significance ★ same residue
NDE1 p.Arg262Trp Uncertain significance ★★ ⚠ same condition
NDE1 p.Arg275Trp Uncertain significance ★★ ⚠ same condition
NDE1 p.Arg37Gln Uncertain significance ★★ ⚠ same condition
NDE1 p.Arg62Gly Uncertain significance ★★ ⚠ same condition
NDE1 p.Asp259Glu Uncertain significance ★★ ⚠ same condition
NDE1 p.Glu34Gly Uncertain significance ★★ ⚠ same condition
NDE1 p.Lys270Arg 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-phe39ser (accessed [today's date]).

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