Is MED25 p.Phe32= (c.96C>T) pathogenic?

MED25 p.Phe32= (c.96C>T) is classified Benign in MED25 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Rare (popmax 0.809%, eas); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with MED25 p.Phe32= (c.96C>T)?

MED25 p.Phe32= (c.96C>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is MED25 p.Phe32= (c.96C>T) in the general population?

MED25 p.Phe32= (c.96C>T) is rare (popmax 0.809%, eas) (gnomAD).

MED25 p.Phe32=

c.96C>T · rs138246339 · VCV699950

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.809%, eas)

Conditions

Charcot-Marie-Tooth disease type 2

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 1.5	GERP -0.75, phastCons 1
Overall
CADD	15.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.809% East Asian · 363/44,872 alleles

Filtering AF 0.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.713%

Overall 0.0228% 368/1,614,108 alleles · rare exomes 354/1,461,822 · genomes 14/152,286 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.809%	124
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.0011%	91,088

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: MED25
Protein: p.Phe32=
Coding: c.96C>T
MANE Select: NM_030973
dbSNP: rs138246339
Type: single nucleotide variant
Location: chr19:49818437 (GRCh38)
Gene constraint: LOEUF 0.874 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.18 · 10 PDB
Residue 32: the 'interaction with the mediator complex' region; an α-helix

Full MED25 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MED25 p.Arg140Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
MED25 c.1101+4G>A Uncertain significance ★★ same condition
MED25 c.135-3C>T Uncertain significance ★★ same condition
MED25 p.Ala190Val Uncertain significance ★★ same condition
MED25 p.Ala251Thr Uncertain significance ★★ ⚠ same condition
MED25 p.Ala255Gly Uncertain significance ★★ ⚠ same condition
MED25 p.Ala364Thr Uncertain significance ★★ ⚠ same condition
MED25 p.Ala401Val 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/med25-p-phe32 (accessed [today's date]).

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