Is DBR1 p.Thr482Met (c.1445C>T) pathogenic?

DBR1 p.Thr482Met (c.1445C>T) is classified Uncertain significance in DBR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-02). AlphaMissense: likely benign (0.0831); Ultra-rare (popmax 0.0891%, eas).

How common is DBR1 p.Thr482Met (c.1445C>T) in the general population?

DBR1 p.Thr482Met (c.1445C>T) is ultra-rare (popmax 0.0891%, eas) (gnomAD).

What do computational predictors say about DBR1 p.Thr482Met (c.1445C>T)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

DBR1 p.Thr482Met

c.1445C>T · rs118174683 · VCV2413271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 490 bp · p 0.31 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0891% East Asian · 40/44,878 alleles

Filtering AF 0.0673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.00632% 102/1,614,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0891%	1,122
South Asian	0.0132%	7,590
Remaining individualsnot grpmax-eligible	0.0112%	8,930
African / African-American	0.00667%	15,000
European (non-Finnish)	0.00322%	31,053

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.Thr482Met
Coding: c.1445C>T
MANE Select: NM_016216
dbSNP: rs118174683
Type: single nucleotide variant
Location: chr3:138162079 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04
Residue 482: 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

Similar variants

DBR1 p.Thr482= Likely benign ★★ same residue
DBR1 c.489+5G>A Uncertain significance ★★ same type
DBR1 p.Ala233Thr Uncertain significance ★★ ⚠ same type
DBR1 p.Ala443Thr Uncertain significance ★★ ⚠ same type
DBR1 p.Ala458Asp Uncertain significance ★★ ⚠ same type
DBR1 p.Arg197Gln Uncertain significance ★★ ⚠ same type
DBR1 p.Arg197Ter Uncertain significance ★★ same type
DBR1 p.Arg527Ser 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/dbr1-p-thr482met (accessed [today's date]).

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