Is DBR1 p.Thr78Met (c.233C>T) pathogenic?

DBR1 p.Thr78Met (c.233C>T) is classified Conflicting classifications of pathogenicity in DBR1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-01). AlphaMissense: likely pathogenic (0.7603); Very rare (popmax 0.00446%, eas); Associated with encephalitis, acute, infection (viral)-induced, susceptibility to, 11.

What condition is associated with DBR1 p.Thr78Met (c.233C>T)?

DBR1 p.Thr78Met (c.233C>T) is associated with encephalitis, acute, infection (viral)-induced, susceptibility to, 11 (ClinVar).

How common is DBR1 p.Thr78Met (c.233C>T) in the general population?

DBR1 p.Thr78Met (c.233C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DBR1 p.Thr78Met (c.233C>T)?

AlphaMissense predicts likely pathogenic (score 0.7603) — an in-silico prediction, not a clinical call.

DBR1 p.Thr78Met

c.233C>T · rs775757073 · VCV3254747

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7603 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

encephalitis, acute, infection (viral)-induced, susceptibility to, 11

Computational evidence

Protein change
AlphaMissense	0.7603	likely pathogenic
REVEL	0.716	pathogenic-leaning
SaProt	LLR -14.09	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 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 12 kb · p 0.4 · regional, not allelic
Overall
CADD	29.9	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 0.00446% East Asian · 2/44,854 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00285% 46/1,613,344 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,427
European (non-Finnish)	0.00322%	31,042
Remaining individualsnot grpmax-eligible	0.0032%	31,226
Finnishnot grpmax-eligible	0.00313%	31,980
African / African-American	0.00267%	37,426

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.Thr78Met
Coding: c.233C>T
MANE Select: NM_016216
dbSNP: rs775757073
Type: single nucleotide variant
Location: chr3:138173591 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04

Full DBR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

encephalitis, acute, infection (viral)-induced, susceptibility to, 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DBR1 p.Thr78= Likely benign ★★ same residue
DBR1 c.489+5G>A Uncertain significance ★★ same condition
DBR1 p.Ala233Thr Uncertain significance ★★ ⚠ same condition
DBR1 p.Arg197Ter Uncertain significance ★★ same condition
DBR1 p.Arg154Lys Uncertain significance ★ ⚠ same condition
DBR1 p.Ile120Thr Uncertain significance ★ ⚠ same condition
DBR1 p.Tyr67Cys Uncertain significance ★ ⚠ same condition
DBR1 p.Arg197fs Pathogenic ★ 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-thr78met (accessed [today's date]).

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