Is NDE1 p.Arg62Ser (c.186A>C) pathogenic?

NDE1 p.Arg62Ser (c.186A>C) is classified Uncertain significance in NDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-08). AlphaMissense: likely pathogenic (0.752); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NDE1 p.Arg62Ser (c.186A>C)?

NDE1 p.Arg62Ser (c.186A>C) is associated with Inborn genetic diseases (ClinVar).

How common is NDE1 p.Arg62Ser (c.186A>C) in the general population?

NDE1 p.Arg62Ser (c.186A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NDE1 p.Arg62Ser (c.186A>C)?

AlphaMissense predicts likely pathogenic (score 0.752) — an in-silico prediction, not a clinical call.

NDE1 p.Arg62Ser

c.186A>C · VCV4118097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.752	likely pathogenic
REVEL	0.294	indeterminate
SaProt	LLR -9.48	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -5.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 59 kb · p 0.74 · regional, not allelic
Overall
CADD	22.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NDE1
Protein: p.Arg62Ser
Coding: c.186A>C
MANE Select: NM_017668
Type: single nucleotide variant
Location: chr16:15667388 (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 62: 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.Arg62Gly 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.Asp259Glu Uncertain significance ★★ ⚠ same condition
NDE1 p.Glu34Gly Uncertain significance ★★ ⚠ same condition
NDE1 p.Lys270Arg Uncertain significance ★★ ⚠ same condition
NDE1 p.Met193Val 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-arg62ser (accessed [today's date]).

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