Is NDRG1 p.Phe89= (c.267T>C) pathogenic?

NDRG1 p.Phe89= (c.267T>C) is classified Likely benign in NDRG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-30). Very rare (popmax 6.2e-05%); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with NDRG1 p.Phe89= (c.267T>C)?

NDRG1 p.Phe89= (c.267T>C) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is NDRG1 p.Phe89= (c.267T>C) in the general population?

NDRG1 p.Phe89= (c.267T>C) is very rare (popmax 6.2e-05%) (gnomAD).

NDRG1 p.Phe89=

c.267T>C · rs2538069469 · VCV2970965

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

Charcot-Marie-Tooth disease type 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 -0.13	GERP -3.8, phastCons 0.005
Overall
CADD	6.782	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,206 alleles · very rare exomes 1/1,461,860 · genomes 0/152,346 · 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: NDRG1
Protein: p.Phe89=
Coding: c.267T>C
MANE Select: NM_006096
dbSNP: rs2538069469
Type: single nucleotide variant
Location: chr8:133262106 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 1 PDB

Full NDRG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NDRG1 p.Phe89Leu Uncertain significance ★ ⚠ same residue
NDRG1 c.205+1G>A Pathogenic/Likely pathogenic ★★ same condition
NDRG1 c.205+1G>C Pathogenic/Likely pathogenic ★★ same condition
NDRG1 p.Arg148Ter Pathogenic ★★ same condition
NDRG1 p.Lys14Ter Pathogenic/Likely pathogenic ★★ same condition
NDRG1 c.595-6A>G Uncertain significance ★★ same condition
NDRG1 c.699-3C>T Uncertain significance ★★ same condition
NDRG1 c.891+5G>A 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/ndrg1-p-phe89 (accessed [today's date]).

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