Is PARD3 p.Arg504Ter (c.1510C>T) pathogenic?

PARD3 p.Arg504Ter (c.1510C>T) is classified Uncertain significance in PARD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). Very rare (popmax 0.00115%, sas).

How common is PARD3 p.Arg504Ter (c.1510C>T) in the general population?

PARD3 p.Arg504Ter (c.1510C>T) is very rare (popmax 0.00115%, sas) (gnomAD).

PARD3 p.Arg504Ter

c.1510C>T · VCV4907044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00115%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 25
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.54	GERP -4.3, phastCons 0.98
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00115% South Asian · 1/86,606 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000189% 3/1,585,428 alleles · very rare exomes 3/1,433,276 · genomes 0/152,152 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00115%	86,606
European (non-Finnish)	0.000171%	584,621

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.Arg504Ter
Coding: c.1510C>T
MANE Select: NM_001184785
Type: single nucleotide variant
Location: chr10:34377996 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.37 · 1 PDB
Residue 504: the pdz 2 domain

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-arg504ter (accessed [today's date]).

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