Is PARD3 p.Lys981Arg (c.2942A>G) pathogenic?

PARD3 p.Lys981Arg (c.2942A>G) is classified Likely benign in PARD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-10-07). AlphaMissense: likely benign (0.0747); Rare (popmax 0.517%, sas); Associated with PARD3-related disorder.

What condition is associated with PARD3 p.Lys981Arg (c.2942A>G)?

PARD3 p.Lys981Arg (c.2942A>G) is associated with PARD3-related disorder (ClinVar).

How common is PARD3 p.Lys981Arg (c.2942A>G) in the general population?

PARD3 p.Lys981Arg (c.2942A>G) is rare (popmax 0.517%, sas) (gnomAD).

What do computational predictors say about PARD3 p.Lys981Arg (c.2942A>G)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

PARD3 p.Lys981Arg

c.2942A>G · rs200130312 · VCV3053572

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.517%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PARD3-related disorder

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.41	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 0.86	GERP -2.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 406 kb · p 0.14 · regional, not allelic
Overall
CADD	17.53	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 K984R vs ClinVar K981R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.517% South Asian · 471/91,078 alleles

Filtering AF 0.479% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.463%

Overall 0.0443% 715/1,613,980 alleles · rare exomes 671/1,461,680 · genomes 44/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.517%	193
Middle Eastern	0.231%	433
Remaining individualsnot grpmax-eligible	0.048%	2,083
Admixed American	0.0233%	4,287
European (non-Finnish)	0.0156%	6,413
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-American	0.00133%	75,034

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.Lys981Arg
Coding: c.2942A>G
MANE Select: NM_001184785
dbSNP: rs200130312
Type: single nucleotide variant
Location: chr10:34317230 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.37 · 1 PDB
Residue 984 UniProt numbering: the 'interaction with frmd4a' region; the 'disordered' region

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

Disease context

PARD3-related disorder

Similar variants

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
PARD3 p.Asn452Asp 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-lys981arg (accessed [today's date]).

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