Is DBR1 p.Pro472Thr (c.1414C>A) pathogenic?

DBR1 p.Pro472Thr (c.1414C>A) is classified Uncertain significance in DBR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-12). AlphaMissense: likely benign (0.2092); Very rare (popmax 0.00935%, afr); Associated with Inborn genetic diseases.

What condition is associated with DBR1 p.Pro472Thr (c.1414C>A)?

DBR1 p.Pro472Thr (c.1414C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DBR1 p.Pro472Thr (c.1414C>A) in the general population?

DBR1 p.Pro472Thr (c.1414C>A) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about DBR1 p.Pro472Thr (c.1414C>A)?

AlphaMissense predicts likely benign (score 0.2092) — an in-silico prediction, not a clinical call.

DBR1 p.Pro472Thr

c.1414C>A · VCV3699596

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2092 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2092	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -6.58	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 10	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 490 bp · p 0.31 · regional, not allelic
Overall
CADD	25.5	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 0.00935% African / African-American · 7/74,898 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000496% 8/1,613,992 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,700
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Pro472Thr
Coding: c.1414C>A
MANE Select: NM_016216
Type: single nucleotide variant
Location: chr3:138162110 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04
Residue 472: 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.Arg527Ser 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

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-pro472thr (accessed [today's date]).

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