Is PRX p.Tyr77= (c.231C>T) pathogenic?

PRX p.Tyr77= (c.231C>T) is classified Likely benign in PRX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-07). Very rare (popmax 0.00668%, eas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Tyr77= (c.231C>T)?

PRX p.Tyr77= (c.231C>T) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Tyr77= (c.231C>T) in the general population?

PRX p.Tyr77= (c.231C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

PRX p.Tyr77=

c.231C>T · rs752192677 · VCV1135507

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

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 -1.9	GERP -4.4
Overall
CADD	6.752	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,882 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000496% 8/1,613,974 alleles · very rare exomes 6/1,461,780 · genomes 2/152,194 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,961
South Asian	0.00329%	30,364
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Tyr77=
Coding: c.231C>T
MANE Select: NM_181882
dbSNP: rs752192677
Type: single nucleotide variant
Location: chr19:40398770 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 77: the pdz domain; an α-helix

Full PRX 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

PRX p.Tyr77Ter Pathogenic ★★ same residue
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

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-tyr77 (accessed [today's date]).

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