Is PARD3 p.Pro910Gln (c.2729C>A) pathogenic?

PARD3 p.Pro910Gln (c.2729C>A) is classified Pathogenic in PARD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-05-01). AlphaMissense: likely pathogenic (0.9621); Absent from gnomAD v4.1; Associated with neural tube defect.

What condition is associated with PARD3 p.Pro910Gln (c.2729C>A)?

PARD3 p.Pro910Gln (c.2729C>A) is associated with neural tube defect (ClinVar).

How common is PARD3 p.Pro910Gln (c.2729C>A) in the general population?

PARD3 p.Pro910Gln (c.2729C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PARD3 p.Pro910Gln (c.2729C>A)?

AlphaMissense predicts likely pathogenic (score 0.9621) — an in-silico prediction, not a clinical call.

PARD3 p.Pro910Gln

c.2729C>A · rs781461462 · VCV254185

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9621 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

neural tube defect

Computational evidence

Protein change
AlphaMissense	0.9621	likely pathogenic ✓ concordant with ClinVar
REVEL	0.445	indeterminate
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 406 kb · p 0.14 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P913Q vs ClinVar P910Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PARD3
Protein: p.Pro910Gln
Coding: c.2729C>A
MANE Select: NM_001184785
dbSNP: rs781461462
Type: single nucleotide variant
Location: chr10:34331221 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.37 · 1 PDB
Residue 913 UniProt numbering: a UniProt-annotated variant site (in ntd; reduces interaction with prkca; increases phosphorylation; disrupts tight junction formation in epithelial cells); the 'interaction with prkci and prkcz' region

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

Disease context

neural tube defect — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PARD3 p.Pro910= Likely benign same residue
PARD3 p.Arg349His Uncertain significance ★ ⚠ same condition
PARD3 p.Asp780Gly Pathogenic ⚠ 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-pro910gln (accessed [today's date]).

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