Is NDE1 p.Ser211Phe (c.632C>T) pathogenic?

NDE1 p.Ser211Phe (c.632C>T) is classified Uncertain significance in NDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1398); Very rare (popmax 0.0011%, sas); Associated with lissencephaly 4.

What condition is associated with NDE1 p.Ser211Phe (c.632C>T)?

NDE1 p.Ser211Phe (c.632C>T) is associated with lissencephaly 4 (ClinVar).

How common is NDE1 p.Ser211Phe (c.632C>T) in the general population?

NDE1 p.Ser211Phe (c.632C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about NDE1 p.Ser211Phe (c.632C>T)?

AlphaMissense predicts likely benign (score 0.1398) — an in-silico prediction, not a clinical call.

NDE1 p.Ser211Phe

c.632C>T · rs886051724 · VCV318061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1398 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lissencephaly 4

Computational evidence

Protein change
AlphaMissense	0.1398	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -9.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 2.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 59 kb · p 0.74 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0011% South Asian · 1/91,086 alleles

Overall 0.000124% 2/1,614,180 alleles · very rare exomes 2/1,461,882 · genomes 0/152,298 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asiangrpmax	0.0011%	91,086

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser211Phe
Coding: c.632C>T
MANE Select: NM_017668
dbSNP: rs886051724
Type: single nucleotide variant
Location: chr16:15691252 (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 211: a modified residue (phosphoserine); the 'interaction with cenpf' region; the 'disordered' 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.Ser211= Likely benign ★ same residue
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

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-ser211phe (accessed [today's date]).

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