Is DDB1 p.Pro572Arg (c.1715C>G) pathogenic?

DDB1 p.Pro572Arg (c.1715C>G) is classified Uncertain significance in DDB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-16). AlphaMissense: likely pathogenic (0.9107); Very rare (popmax 0.005%, amr).

How common is DDB1 p.Pro572Arg (c.1715C>G) in the general population?

DDB1 p.Pro572Arg (c.1715C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about DDB1 p.Pro572Arg (c.1715C>G)?

AlphaMissense predicts likely pathogenic (score 0.9107) — an in-silico prediction, not a clinical call.

DDB1 p.Pro572Arg

c.1715C>G · VCV4869602

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9107 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9107	likely pathogenic
REVEL	0.648	pathogenic-leaning
SaProt	LLR -15.36	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 7,478 bp · p 1.9e-11 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,986 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,613,894 alleles · very rare exomes 0/1,461,852 · genomes 3/152,042 · joint denominator

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: DDB1
Protein: p.Pro572Arg
Coding: c.1715C>G
MANE Select: NM_001923
Type: single nucleotide variant
Location: chr11:61314085 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 219 PDB
Residue 572: a turn; the 'interaction with cdt1' region; the 'wd repeat beta-propeller b; interaction with cul4a' region

Full DDB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDB1 p.Pro572Ser Uncertain significance ★★ ⚠ same residue
DDB1 p.Arg188Trp Pathogenic/Likely pathogenic ★★ same type
DDB1 p.Glu1135Asp Uncertain significance ★★ same type
DDB1 p.Ile558Phe Uncertain significance ★★ ⚠ same type
DDB1 p.Ile793Thr Uncertain significance ★★ ⚠ same type
DDB1 p.Met534Leu Uncertain significance ★★ ⚠ same type
DDB1 p.Val1109Ala Uncertain significance ★★ ⚠ same type
DDB1 p.Val500Met 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/ddb1-p-pro572arg (accessed [today's date]).

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