Is PRX p.Ala367Asp (c.1100C>A) pathogenic?

PRX p.Ala367Asp (c.1100C>A) is classified Uncertain significance in PRX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-08). AlphaMissense: ambiguous (0.5484); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with PRX p.Ala367Asp (c.1100C>A)?

PRX p.Ala367Asp (c.1100C>A) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Ala367Asp (c.1100C>A) in the general population?

PRX p.Ala367Asp (c.1100C>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about PRX p.Ala367Asp (c.1100C>A)?

AlphaMissense predicts ambiguous (score 0.5484) — an in-silico prediction, not a clinical call.

PRX p.Ala367Asp

c.1100C>A · rs143400291 · VCV543361

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5484 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5484	ambiguous
REVEL	0.116	moderately benign-leaning
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -1.1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.97 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,008 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.0018% 29/1,613,708 alleles · very rare exomes 26/1,461,486 · genomes 3/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,004
European (non-Finnish)	0.0022%	45,386
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Ala367Asp
Coding: c.1100C>A
MANE Select: NM_181882
dbSNP: rs143400291
Type: single nucleotide variant
Location: chr19:40397252 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 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-ala367asp (accessed [today's date]).

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