Is PRX p.Ala612= (c.1836C>T) pathogenic?

PRX p.Ala612= (c.1836C>T) is classified Benign/Likely benign in PRX (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). Rare (popmax 0.314%, sas); Associated with Inborn genetic diseases.

What condition is associated with PRX p.Ala612= (c.1836C>T)?

PRX p.Ala612= (c.1836C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4F, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Ala612= (c.1836C>T) in the general population?

PRX p.Ala612= (c.1836C>T) is rare (popmax 0.314%, sas) (gnomAD).

PRX p.Ala612=

c.1836C>T · rs574899855 · VCV215546

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.314%, sas)

Conditions

Inborn genetic diseases

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 -20	GERP -3.1
Overall
CADD	0.046	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.314% South Asian · 285/90,826 alleles

Filtering AF 0.284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.272%

Overall 0.027% 434/1,608,958 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.314%	319
Remaining individualsnot grpmax-eligible	0.024%	4,161
Middle Eastern	0.0166%	6,034
European (non-Finnish)	0.0104%	9,661
African / African-American	0.0082%	12,199
East Asian	0.00449%	22,288
Finnishnot grpmax-eligible	0.00316%	31,693
Admixed American	0.00168%	59,492

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.Ala612=
Coding: c.1836C>T
MANE Select: NM_181882
dbSNP: rs574899855
Type: single nucleotide variant
Location: chr19:40396516 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 612: the '55 x 5 aa approximate tandem repeats of [lvmag]-[psreqc]-[edkl]-[livmap]-[aqkhrpe]; that may have a tripeptide spacer of [lv]-p-[ker]' region

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

Disease context

Inborn genetic diseases — 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 p.Ala612Thr Uncertain significance ★★ ⚠ 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-ala612 (accessed [today's date]).

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