Is PARD3 p.Arg381Cys (c.1141C>T) pathogenic?

PARD3 p.Arg381Cys (c.1141C>T) is classified Uncertain significance in PARD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). AlphaMissense: likely benign (0.0853); Ultra-rare (popmax 0.0253%, sas).

How common is PARD3 p.Arg381Cys (c.1141C>T) in the general population?

PARD3 p.Arg381Cys (c.1141C>T) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about PARD3 p.Arg381Cys (c.1141C>T)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

PARD3 p.Arg381Cys

c.1141C>T · VCV4829974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -9.06	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 4.5	GERP 0.073, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 406 kb · p 0.14 · regional, not allelic
Overall
CADD	21.4	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 0.0253% South Asian · 23/91,074 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00229% 37/1,614,134 alleles · ultra-rare exomes 37/1,461,886 · genomes 0/152,248 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.000932%	107,275

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.Arg381Cys
Coding: c.1141C>T
MANE Select: NM_001184785
Type: single nucleotide variant
Location: chr10:34382798 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.37 · 1 PDB

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

Similar variants

PARD3 p.Arg381His Uncertain significance ★ ⚠ same residue
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

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-arg381cys (accessed [today's date]).

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