Is PARD3 p.Arg50His (c.149G>A) pathogenic?

PARD3 p.Arg50His (c.149G>A) is classified Uncertain significance in PARD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely benign (0.2265); Ultra-rare (popmax 0.0134%, eas).

How common is PARD3 p.Arg50His (c.149G>A) in the general population?

PARD3 p.Arg50His (c.149G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about PARD3 p.Arg50His (c.149G>A)?

AlphaMissense predicts likely benign (score 0.2265) — an in-silico prediction, not a clinical call.

PARD3 p.Arg50His

c.149G>A · VCV4130936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2265 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2265	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -7.82	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 5.9	phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 179 kb · p 0.00019 · regional, not allelic
Overall
CADD	26.0	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 0.0134% East Asian · 6/44,842 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.0013% 21/1,610,672 alleles · ultra-rare exomes 19/1,458,538 · genomes 2/152,134 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,474
South Asian	0.0055%	18,198
Remaining individualsnot grpmax-eligible	0.0016%	62,406
African / African-American	0.00133%	74,922
European (non-Finnish)	0.00068%	147,124

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.Arg50His
Coding: c.149G>A
MANE Select: NM_001184785
Type: single nucleotide variant
Location: chr10:34696391 (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 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-arg50his (accessed [today's date]).

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