Is PRX p.Thr102= (c.306C>T) pathogenic?

PRX p.Thr102= (c.306C>T) is classified Benign/Likely benign in PRX (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 19.2%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Charcot-Marie-Tooth disease.

What condition is associated with PRX p.Thr102= (c.306C>T)?

PRX p.Thr102= (c.306C>T) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 4F, Charcot-Marie-Tooth disease type 4 (ClinVar).

PRX p.Thr102=

Q: How common is PRX p.Thr102= (c.306C>T) in the general population?

PRX p.Thr102= (c.306C>T) is common (popmax 19.2%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.306C>T · rs744389 · VCV130051

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 19.2%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

Charcot-Marie-Tooth disease

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 -0.5	GERP -3.7, phastCons 0.003
Overall
CADD	11.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.2% European (non-Finnish) · 226,319/1,179,914 alleles

Filtering AF 19.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.1%

Overall 17% 274,903/1,613,946 alleles · common exomes 255,736/1,461,722 · genomes 19,167/152,224 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	19.2%	5
Amishnot grpmax-eligible	18.9%	5
South Asian	18.8%	5
Remaining individualsnot grpmax-eligible	15.9%	6
Finnishnot grpmax-eligible	14.3%	7
Middle Eastern	11.3%	9
Ashkenazi Jewishnot grpmax-eligible	9.9%	10
Admixed American	7.98%	13
African / African-American	3.73%	27
East Asian	2.4%	42

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: PRX
Protein: p.Thr102=
Coding: c.306C>T
MANE Select: NM_181882
dbSNP: rs744389
Type: single nucleotide variant
Location: chr19:40398695 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB

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

Disease context

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

Also linked: Charcot-Marie-Tooth disease type 4F Charcot-Marie-Tooth disease type 4

Similar variants

PRX c.184+2T>C Likely pathogenic ★★ same condition
PRX p.Arg1070Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Arg196Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Arg364Ter Pathogenic ★★ same condition
PRX p.Arg368Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Arg392Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Arg464Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Arg897Ter Pathogenic/Likely pathogenic ★★ 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/prx-p-thr102 (accessed [today's date]).

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