Is PIDD1 p.Arg490= (c.1470A>G) pathogenic?

PIDD1 p.Arg490= (c.1470A>G) is classified Likely benign in PIDD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). Ultra-rare (popmax 0.0208%, eas).

How common is PIDD1 p.Arg490= (c.1470A>G) in the general population?

PIDD1 p.Arg490= (c.1470A>G) is ultra-rare (popmax 0.0208%, eas) (gnomAD).

PIDD1 p.Arg490=

c.1470A>G · VCV4910132

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.51	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -8.4	GERP -2.8
Overall
CADD	8.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0208% East Asian · 9/43,264 alleles

Filtering AF 0.0108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00805%

Overall 0.00298% 46/1,543,538 alleles · ultra-rare exomes 41/1,391,242 · genomes 5/152,296 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0271%	3,687
East Asiangrpmax	0.0208%	4,807
Middle Eastern	0.0172%	5,824
Remaining individualsnot grpmax-eligible	0.0084%	11,908
South Asian	0.0037%	27,007
European (non-Finnish)	0.00184%	54,402

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PIDD1
Protein: p.Arg490=
Coding: c.1470A>G
MANE Select: NM_145886
Type: single nucleotide variant
Location: chr11:801457 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.02 · 2 PDB
Residue 490: the zu5 2 domain; a UniProt-annotated variant site (in mrt75)

Full PIDD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PIDD1 p.Arg637Ter Pathogenic/Likely pathogenic ★★ same type
PIDD1 p.Arg862Trp Pathogenic ★★ same type
PIDD1 p.Arg551Cys Uncertain significance ★★ ⚠ same type
PIDD1 p.Arg605Gln Uncertain significance ★★ ⚠ same type
PIDD1 p.Arg725Cys Uncertain significance ★★ same type
PIDD1 p.Arg742Ser Uncertain significance ★★ ⚠ same type
PIDD1 p.Arg821Trp Uncertain significance ★★ ⚠ same type
PIDD1 p.Arg842His 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/pidd1-p-arg490 (accessed [today's date]).

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