Is PARD3 p.Cys191Trp (c.573C>G) pathogenic?

PARD3 p.Cys191Trp (c.573C>G) is classified Uncertain significance in PARD3 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.1397); Very rare (popmax 0.00171%, amr); Associated with prostate cancer.

What condition is associated with PARD3 p.Cys191Trp (c.573C>G)?

PARD3 p.Cys191Trp (c.573C>G) is associated with prostate cancer (ClinVar).

How common is PARD3 p.Cys191Trp (c.573C>G) in the general population?

PARD3 p.Cys191Trp (c.573C>G) is very rare (popmax 0.00171%, amr) (gnomAD).

What do computational predictors say about PARD3 p.Cys191Trp (c.573C>G)?

AlphaMissense predicts likely benign (score 0.1397) — an in-silico prediction, not a clinical call.

PARD3 p.Cys191Trp

c.573C>G · rs193920776 · VCV161556

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer

Computational evidence

Protein change
AlphaMissense	0.1397	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -5.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.14	GERP -4.1, phastCons 0.007
Regional constraint	o/e 0.96	unconstrained · MANE · 406 kb · p 0.14 · regional, not allelic
Overall
CADD	17.2	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

Grpmax group 0.00171% Admixed American · 1/58,502 alleles

Overall 0.000125% 2/1,601,026 alleles · very rare exomes 1/1,449,034 · genomes 1/151,992 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00171%	58,502
European (non-Finnish)	8.52e-05%	1,173,216

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: PARD3
Protein: p.Cys191Trp
Coding: c.573C>G
MANE Select: NM_001184785
dbSNP: rs193920776
Type: single nucleotide variant
Location: chr10:34470094 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.37 · 1 PDB
Residue 191: the 'disordered' region

Full PARD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

prostate cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PARD3 p.Cys191Phe Uncertain significance ⚠ same residue
PARD3 p.Cys191= Likely benign same residue
PARD3 p.Met228Ile Uncertain significance ⚠ same condition
PARD3 c.2560+10A>G Benign ★★ same type
PARD3 p.Ala934Val Benign ★★ same type
PARD3 p.Glu107Asp Benign ★★ same type
PARD3 p.Glu1252= Benign/Likely benign ★★ same type
PARD3 p.Ser798Asn Benign ★★ same type

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/pard3-p-cys191trp (accessed [today's date]).

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