Is PIDD1 p.Phe672= (c.2016C>T) pathogenic?

PIDD1 p.Phe672= (c.2016C>T) is classified Likely benign in PIDD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). Ultra-rare (popmax 0.0912%, nfe).

How common is PIDD1 p.Phe672= (c.2016C>T) in the general population?

PIDD1 p.Phe672= (c.2016C>T) is ultra-rare (popmax 0.0912%, nfe) (gnomAD).

PIDD1 p.Phe672=

c.2016C>T · VCV4533752

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0912%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5	GERP -2.4
Overall
CADD	0.265	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0912% European (non-Finnish) · 1,075/1,179,336 alleles

Filtering AF 0.0866% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0847%

Overall 0.0832% 1,338/1,608,482 alleles · ultra-rare exomes 1,232/1,456,214 · genomes 106/152,268 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.341%	293
European (non-Finnish)grpmax	0.0912%	1,097
Remaining individualsnot grpmax-eligible	0.0689%	1,452
East Asian	0.0134%	7,479
African / African-American	0.00933%	10,716
Admixed American	0.00667%	14,997
South Asian	0.0011%	90,990

Finnish 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.Phe672=
Coding: c.2016C>T
MANE Select: NM_145886
Type: single nucleotide variant
Location: chr11:800568 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.02 · 2 PDB
Residue 672: the 'upa domain' region; 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-phe672 (accessed [today's date]).

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