Is DDB2 p.Arg214Ter (c.640C>T) pathogenic?

DDB2 p.Arg214Ter (c.640C>T) is classified Pathogenic in DDB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-19). Very rare (popmax 0.00167%, amr).

How common is DDB2 p.Arg214Ter (c.640C>T) in the general population?

DDB2 p.Arg214Ter (c.640C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

DDB2 p.Arg214Ter

c.640C>T · rs144989465 · VCV2062799

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.3, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,972 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00124% 20/1,613,912 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,972
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.00153%	65,555

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.Arg214Ter
Coding: c.640C>T
MANE Select: NM_000107
dbSNP: rs144989465
Type: single nucleotide variant
Location: chr11:47234610 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.69 · 10 PDB
Residue 214: a turn

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-arg214ter (accessed [today's date]).

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