Is DBR1 p.Ile126Val (c.376A>G) pathogenic?

DBR1 p.Ile126Val (c.376A>G) is classified Uncertain significance in DBR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: likely pathogenic (0.887); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with DBR1 p.Ile126Val (c.376A>G)?

DBR1 p.Ile126Val (c.376A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DBR1 p.Ile126Val (c.376A>G) in the general population?

DBR1 p.Ile126Val (c.376A>G) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about DBR1 p.Ile126Val (c.376A>G)?

AlphaMissense predicts likely pathogenic (score 0.887) — an in-silico prediction, not a clinical call.

DBR1 p.Ile126Val

c.376A>G · rs757813538 · VCV2489792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.887 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.887	likely pathogenic
REVEL	0.453	indeterminate
SaProt	LLR -9.84	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 5.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 12 kb · p 0.4 · regional, not allelic
Overall
CADD	25.4	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 0.0156% East Asian · 7/44,846 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000558% 9/1,613,508 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,407
Remaining individualsnot grpmax-eligible	0.0032%	31,239

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.Ile126Val
Coding: c.376A>G
MANE Select: NM_016216
dbSNP: rs757813538
Type: single nucleotide variant
Location: chr3:138171660 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04
Residue 126: the 'lariat recognition loop' region

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.Ile126= Likely benign ★ same residue
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

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-ile126val (accessed [today's date]).

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