Is PRX p.Pro89Ser (c.265C>T) pathogenic?

PRX p.Pro89Ser (c.265C>T) is classified Uncertain significance in PRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-12-02). AlphaMissense: likely pathogenic (0.9504); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with PRX p.Pro89Ser (c.265C>T)?

PRX p.Pro89Ser (c.265C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRX p.Pro89Ser (c.265C>T) in the general population?

PRX p.Pro89Ser (c.265C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PRX p.Pro89Ser (c.265C>T)?

AlphaMissense predicts likely pathogenic (score 0.9504) — an in-silico prediction, not a clinical call.

PRX p.Pro89Ser

c.265C>T · rs550049072 · VCV1310221

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9504	likely pathogenic · top 1% in PRX
REVEL	0.588	indeterminate
SaProt	LLR -5.50	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.97 · regional, not allelic
Overall
CADD	28.8	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 0.00223% East Asian · 1/44,878 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,092 alleles · very rare exomes 3/1,461,796 · genomes 1/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
European (non-Finnish)	0.000254%	393,318

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.Pro89Ser
Coding: c.265C>T
MANE Select: NM_181882
dbSNP: rs550049072
Type: single nucleotide variant
Location: chr19:40398736 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 89: the pdz domain

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

Similar variants

PRX c.184+2T>C Likely pathogenic ★★ same condition
PRX p.Arg368Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Cys715Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Tyr77Ter Pathogenic ★★ same condition
PRX p.Ala1036Val Uncertain significance ★★ ⚠ same condition
PRX p.Ala1074Thr Uncertain significance ★★ ⚠ same condition
PRX p.Ala1289Asp Uncertain significance ★★ ⚠ same condition
PRX p.Ala1384Val 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/prx-p-pro89ser (accessed [today's date]).

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