Is DDB2 p.Pro298= (c.894C>T) pathogenic?

DDB2 p.Pro298= (c.894C>T) is classified Likely benign in DDB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). Very rare (popmax 0.00585%, nfe).

How common is DDB2 p.Pro298= (c.894C>T) in the general population?

DDB2 p.Pro298= (c.894C>T) is very rare (popmax 0.00585%, nfe) (gnomAD).

DDB2 p.Pro298=

c.894C>T · rs137958929 · VCV749088

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00585%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.201	benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.1	GERP -4.4
Overall
CADD	4.531	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00585% European (non-Finnish) · 69/1,180,042 alleles

Filtering AF 0.0047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.00539% 87/1,614,212 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.016%	6,251
European (non-Finnish)grpmax	0.00585%	17,102
East Asian	0.00446%	22,441
African / African-American	0.004%	25,018
South Asian	0.0022%	45,542
Admixed American	0.00167%	60,026

Remaining individuals 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: DDB2
Protein: p.Pro298=
Coding: c.894C>T
MANE Select: NM_000107
dbSNP: rs137958929
Type: single nucleotide variant
Location: chr11:47235283 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.69 · 10 PDB

Full DDB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDB2 c.702+1G>T Pathogenic/Likely pathogenic ★★ same type
DDB2 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same type
DDB2 p.Arg273His Pathogenic/Likely pathogenic ★★ same type
DDB2 p.Arg355Ter Pathogenic ★★ same type
DDB2 p.Arg332His Uncertain significance ★★ ⚠ same type
DDB2 p.Cys66Gly Uncertain significance ★★ ⚠ same type
DDB2 p.Glu178Ala Uncertain significance ★★ ⚠ same type
DDB2 p.Leu350Pro 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/ddb2-p-pro298 (accessed [today's date]).

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