Is PIDD1 p.Pro482Ser (c.1444C>T) pathogenic?

PIDD1 p.Pro482Ser (c.1444C>T) is classified Likely benign in PIDD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-25). AlphaMissense: likely benign (0.0972); Very rare (popmax 0.00122%, sas); Associated with Inborn genetic diseases.

What condition is associated with PIDD1 p.Pro482Ser (c.1444C>T)?

PIDD1 p.Pro482Ser (c.1444C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PIDD1 p.Pro482Ser (c.1444C>T) in the general population?

PIDD1 p.Pro482Ser (c.1444C>T) is very rare (popmax 0.00122%, sas) (gnomAD).

What do computational predictors say about PIDD1 p.Pro482Ser (c.1444C>T)?

AlphaMissense predicts likely benign (score 0.0972) — an in-silico prediction, not a clinical call.

PIDD1 p.Pro482Ser

c.1444C>T · VCV4832483

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0972 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00122%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0972	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	15.8	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 0.00122% South Asian · 1/82,120 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000194% 3/1,546,798 alleles · very rare exomes 3/1,394,444 · genomes 0/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00122%	82,120
European (non-Finnish)	0.000175%	572,059

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.Pro482Ser
Coding: c.1444C>T
MANE Select: NM_145886
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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIDD1 p.Pro482Leu Uncertain significance ★ ⚠ same residue
PIDD1 p.Pro482Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
PIDD1 p.Arg551Cys Uncertain significance ★★ ⚠ same condition
PIDD1 p.Arg605Gln Uncertain significance ★★ ⚠ same condition
PIDD1 p.Arg742Ser Uncertain significance ★★ ⚠ same condition
PIDD1 p.Arg821Trp Uncertain significance ★★ ⚠ same condition
PIDD1 p.Arg842His Uncertain significance ★★ ⚠ same condition
PIDD1 p.Arg93His Uncertain significance ★★ ⚠ same condition

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-pro482ser (accessed [today's date]).

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