Is DBR1 p.Arg527Ser (c.1581G>T) pathogenic?

DBR1 p.Arg527Ser (c.1581G>T) is classified Uncertain significance in DBR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-26). AlphaMissense: likely pathogenic (0.9989); Ultra-rare (popmax 0.0417%, amr); Associated with Inborn genetic diseases.

What condition is associated with DBR1 p.Arg527Ser (c.1581G>T)?

DBR1 p.Arg527Ser (c.1581G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DBR1 p.Arg527Ser (c.1581G>T) in the general population?

DBR1 p.Arg527Ser (c.1581G>T) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

What do computational predictors say about DBR1 p.Arg527Ser (c.1581G>T)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

DBR1 p.Arg527Ser

c.1581G>T · rs201982495 · VCV2201668

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic · top 2% in DBR1
REVEL	0.293	indeterminate
SaProt	LLR -6.27	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 490 bp · p 0.31 · regional, not allelic
Overall
CADD	23.4	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 0.0417% Admixed American · 25/59,998 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.0116% 188/1,614,078 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,400
European (non-Finnish)	0.0131%	7,613
Remaining individualsnot grpmax-eligible	0.0096%	10,415
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-American	0.00133%	74,940

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: DBR1
Protein: p.Arg527Ser
Coding: c.1581G>T
MANE Select: NM_016216
dbSNP: rs201982495
Type: single nucleotide variant
Location: chr3:138161943 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04
Residue 527: the 'disordered' region; a UniProt-annotated variant site (in iiae11; loss of protein expression)

Full DBR1 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

DBR1 p.Ala233Thr Uncertain significance ★★ ⚠ same condition
DBR1 p.Ala443Thr Uncertain significance ★★ ⚠ same condition
DBR1 p.Ala458Asp Uncertain significance ★★ ⚠ same condition
DBR1 p.Arg197Gln Uncertain significance ★★ ⚠ same condition
DBR1 p.Glu434Asp Uncertain significance ★★ ⚠ same condition
DBR1 p.Gly121Ser Uncertain significance ★★ ⚠ same condition
DBR1 p.Gly27Ser Uncertain significance ★★ ⚠ same condition
DBR1 p.Gly494Ala 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/dbr1-p-arg527ser (accessed [today's date]).

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