Is PARD3 p.Thr786= (c.2358G>A) pathogenic?

PARD3 p.Thr786= (c.2358G>A) is classified Likely benign in PARD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-20). Ultra-rare (popmax 0.0165%, mid); Associated with PARD3-related disorder.

What condition is associated with PARD3 p.Thr786= (c.2358G>A)?

PARD3 p.Thr786= (c.2358G>A) is associated with PARD3-related disorder (ClinVar).

How common is PARD3 p.Thr786= (c.2358G>A) in the general population?

PARD3 p.Thr786= (c.2358G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

PARD3 p.Thr786=

c.2358G>A · rs774456144 · VCV3050779

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

PARD3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -12	GERP -3.7
Overall
CADD	0.132	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00316% 51/1,613,784 alleles · ultra-rare exomes 43/1,461,642 · genomes 8/152,142 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
African / African-American	0.00668%	14,979
Remaining individualsnot grpmax-eligible	0.0064%	15,619
Admixed American	0.005%	19,988
European (non-Finnish)	0.00305%	32,776
South Asian	0.0022%	45,520

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.Thr786=
Coding: c.2358G>A
MANE Select: NM_001184785
dbSNP: rs774456144
Type: single nucleotide variant
Location: chr10:34341677 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.37 · 1 PDB
Residue 786: the 'interaction with prkci and prkcz' region

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

Disease context

PARD3-related disorder

Similar variants

PARD3 p.Thr786Met Uncertain significance ★ ⚠ same residue
PARD3 c.2068-7T>C Likely benign same condition
PARD3 c.3419+8C>T Likely benign same condition
PARD3 c.715-4C>T Likely benign same condition
PARD3 c.*4C>T Benign same condition
PARD3 p.Ala93= Likely benign same condition
PARD3 p.Arg1191= Benign same condition
PARD3 p.Arg987= Likely benign 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/pard3-p-thr786 (accessed [today's date]).

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