Is PARD3 p.Arg204Trp (c.610C>T) pathogenic?

PARD3 p.Arg204Trp (c.610C>T) is classified Uncertain significance in PARD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: ambiguous (0.3466); Very rare (popmax 0.0066%, sas).

How common is PARD3 p.Arg204Trp (c.610C>T) in the general population?

PARD3 p.Arg204Trp (c.610C>T) is very rare (popmax 0.0066%, sas) (gnomAD).

What do computational predictors say about PARD3 p.Arg204Trp (c.610C>T)?

AlphaMissense predicts ambiguous (score 0.3466) — an in-silico prediction, not a clinical call.

PARD3 p.Arg204Trp

c.610C>T · rs199838013 · VCV2221358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3466 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0066%, sas)

Computational evidence

Protein change
AlphaMissense	0.3466	ambiguous
REVEL	0.331	indeterminate
SaProt	LLR -10.47	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.5	GERP -1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 406 kb · p 0.14 · regional, not allelic
Overall
CADD	23.6	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 0.0066% South Asian · 6/90,862 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00397% 64/1,613,112 alleles · very rare exomes 59/1,460,978 · genomes 5/152,134 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0066%	15,144
Finnishnot grpmax-eligible	0.00625%	16,006
European (non-Finnish)	0.00432%	23,132
Admixed American	0.00167%	59,848
Remaining individualsnot grpmax-eligible	0.0016%	62,440
African / African-American	0.00134%	74,880

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.Arg204Trp
Coding: c.610C>T
MANE Select: NM_001184785
dbSNP: rs199838013
Type: single nucleotide variant
Location: chr10:34450421 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.37 · 1 PDB
Residue 204: 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-arg204trp (accessed [today's date]).

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