Is PRX p.Ser56Ile (c.167G>T) pathogenic?

PRX p.Ser56Ile (c.167G>T) is classified Uncertain significance in PRX (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-24). AlphaMissense: likely benign (0.2926); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PRX p.Ser56Ile (c.167G>T)?

PRX p.Ser56Ile (c.167G>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRX p.Ser56Ile (c.167G>T) in the general population?

PRX p.Ser56Ile (c.167G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRX p.Ser56Ile (c.167G>T)?

AlphaMissense predicts likely benign (score 0.2926) — an in-silico prediction, not a clinical call.

PRX p.Ser56Ile

c.167G>T · rs769996704 · VCV1777882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2926 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,562,974)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2926	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -2.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.97 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,562,974). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRX
Protein: p.Ser56Ile
Coding: c.167G>T
MANE Select: NM_181882
dbSNP: rs769996704
Type: single nucleotide variant
Location: chr19:40403723 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 56: the pdz domain; an α-helix

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 p.Ser56= Likely benign ★ same residue
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

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-ser56ile (accessed [today's date]).

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