Is PIDD1 p.Pro482Ala (c.1444C>G) pathogenic?

PIDD1 p.Pro482Ala (c.1444C>G) is classified Conflicting classifications of pathogenicity in PIDD1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-01). AlphaMissense: likely benign (0.0613); Rare (popmax 0.121%, nfe).

How common is PIDD1 p.Pro482Ala (c.1444C>G) in the general population?

PIDD1 p.Pro482Ala (c.1444C>G) is rare (popmax 0.121%, nfe) (gnomAD).

What do computational predictors say about PIDD1 p.Pro482Ala (c.1444C>G)?

AlphaMissense predicts likely benign (score 0.0613) — an in-silico prediction, not a clinical call.

PIDD1 p.Pro482Ala

c.1444C>G · rs201920329 · VCV2581674

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0613 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0613	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -7.65	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 1.1	GERP -1.1, phastCons 0.59
Regional constraint	o/e 1.08	unconstrained · MANE · 5,078 bp · p 0.0041 · regional, not allelic
Overall
CADD	7.97	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 0.121% European (non-Finnish) · 1,386/1,144,124 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.114%

Overall 0.0958% 1,482/1,546,680 alleles · rare exomes 1,384/1,394,444 · genomes 98/152,236 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.121%	825
Remaining individualsnot grpmax-eligible	0.0737%	1,357
Admixed American	0.0636%	1,574
African / African-American	0.019%	5,253
Finnishnot grpmax-eligible	0.00507%	19,707
East Asian	0.00468%	21,375

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.Pro482Ala
Coding: c.1444C>G
MANE Select: NM_145886
dbSNP: rs201920329
Type: single nucleotide variant
Location: chr11:801483 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.02 · 2 PDB
Residue 482: 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.Pro482Leu Uncertain significance ★ ⚠ same residue
PIDD1 p.Pro482Ser Likely benign ★ same residue
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

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-pro482ala (accessed [today's date]).

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