Is MED25 p.Pro640= (c.1920T>C) pathogenic?

MED25 p.Pro640= (c.1920T>C) is classified Likely benign in MED25 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-18). Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with MED25 p.Pro640= (c.1920T>C)?

MED25 p.Pro640= (c.1920T>C) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is MED25 p.Pro640= (c.1920T>C) in the general population?

MED25 p.Pro640= (c.1920T>C) is absent from gnomAD v4.1 (gnomAD).

MED25 p.Pro640=

c.1920T>C · rs1600331507 · VCV793146

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.012	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.2	GERP -3.1
Overall
CADD	3.926	PHRED · no single calibrated threshold — expert panels disagree

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: MED25
Protein: p.Pro640=
Coding: c.1920T>C
MANE Select: NM_030973
dbSNP: rs1600331507
Type: single nucleotide variant
Location: chr19:49835900 (GRCh38)
Gene constraint: LOEUF 0.874 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.18 · 10 PDB
Residue 640: the 'disordered' region; the 'interaction with rara' region

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.Pro640fs Conflicting classifications of pathogenicity ★ same residue
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

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-pro640 (accessed [today's date]).

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