Is PARD3 p.Gly97Ser (c.289G>A) pathogenic?

PARD3 p.Gly97Ser (c.289G>A) is classified Uncertain significance in PARD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: likely pathogenic (0.6884); Very rare (popmax 6.2e-05%).

How common is PARD3 p.Gly97Ser (c.289G>A) in the general population?

PARD3 p.Gly97Ser (c.289G>A) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about PARD3 p.Gly97Ser (c.289G>A)?

AlphaMissense predicts likely pathogenic (score 0.6884) — an in-silico prediction, not a clinical call.

PARD3 p.Gly97Ser

c.289G>A · VCV3414106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6884 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6884	likely pathogenic
REVEL	0.235	benign-leaning
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 179 kb · p 0.00019 · regional, not allelic
Overall
CADD	24.2	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 6.2e-05%

Overall 6.2e-05% 1/1,614,160 alleles · very rare exomes 1/1,461,850 · genomes 0/152,310 · joint denominator

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.Gly97Ser
Coding: c.289G>A
MANE Select: NM_001184785
Type: single nucleotide variant
Location: chr10:34517093 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.37 · 1 PDB
Residue 97: the 'disordered' region

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

Similar variants

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
ASIP p.Ser72Pro Uncertain significance ★ ⚠ same type
PARD3 p.Ala1062Thr Uncertain significance ★ ⚠ same type
PARD3 p.Ala1337Pro Uncertain significance ★ ⚠ 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-gly97ser (accessed [today's date]).

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