Is PARD3 p.Arg1000Ser (c.3000A>C) pathogenic?

PARD3 p.Arg1000Ser (c.3000A>C) is classified Uncertain significance in PARD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-28). AlphaMissense: ambiguous (0.4939); Rare (popmax 0.108%, afr).

How common is PARD3 p.Arg1000Ser (c.3000A>C) in the general population?

PARD3 p.Arg1000Ser (c.3000A>C) is rare (popmax 0.108%, afr) (gnomAD).

What do computational predictors say about PARD3 p.Arg1000Ser (c.3000A>C)?

AlphaMissense predicts ambiguous (score 0.4939) — an in-silico prediction, not a clinical call.

PARD3 p.Arg1000Ser

c.3000A>C · VCV3414085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4939 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.108%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4939	ambiguous
REVEL	0.113	moderately benign-leaning
SaProt	LLR -7.80	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP 1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 406 kb · p 0.14 · regional, not allelic
Overall
CADD	19.53	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 R1003S vs ClinVar R1000S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.108% African / African-American · 81/74,980 alleles

Filtering AF 0.089% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.082%

Overall 0.00691% 111/1,605,770 alleles · rare exomes 55/1,453,456 · genomes 56/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.108%	926
Remaining individualsnot grpmax-eligible	0.0225%	4,447
Admixed American	0.0205%	4,881
South Asian	0.00446%	22,408

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.Arg1000Ser
Coding: c.3000A>C
MANE Select: NM_001184785
Type: single nucleotide variant
Location: chr10:34317172 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.37 · 1 PDB
Residue 1003 UniProt numbering: the 'interaction with frmd4a' region; 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-arg1000ser (accessed [today's date]).

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