Is DBT p.Ile429Ser (c.1286T>G) pathogenic?

DBT p.Ile429Ser (c.1286T>G) is classified Uncertain significance in DBT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: ambiguous (0.3736); Low-frequency (popmax 1.1%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DBT p.Ile429Ser (c.1286T>G)?

DBT p.Ile429Ser (c.1286T>G) is associated with Inborn genetic diseases (ClinVar).

How common is DBT p.Ile429Ser (c.1286T>G) in the general population?

DBT p.Ile429Ser (c.1286T>G) is low-frequency (popmax 1.1%, nfe) (gnomAD).

What do computational predictors say about DBT p.Ile429Ser (c.1286T>G)?

AlphaMissense predicts ambiguous (score 0.3736) — an in-silico prediction, not a clinical call.

DBT p.Ile429Ser

c.1286T>G · rs1661094407 · VCV2473598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3736 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.1%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3736	ambiguous
REVEL	0.2	benign-leaning
SaProt	LLR -8.31	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	24.8	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 1.1% European (non-Finnish) · 6,733/611,334 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.07%

Overall 0.818% 7,497/916,130 alleles · low-frequency exomes 7,489/807,112 · genomes 8/109,018 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.1%	91
Remaining individualsnot grpmax-eligible	0.771%	130
African / African-American	0.367%	273
Middle Eastern	0.355%	281
Ashkenazi Jewishnot grpmax-eligible	0.286%	350
East Asian	0.19%	527
South Asian	0.184%	545
Finnishnot grpmax-eligible	0.0661%	1,512
Admixed American	0.037%	2,705

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: DBT
Protein: p.Ile429Ser
Coding: c.1286T>G
MANE Select: NM_001918
dbSNP: rs1661094407
Type: single nucleotide variant
Location: chr1:100196418 (GRCh38)
Gene constraint: LOEUF 1.255 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.71 · 5 PDB

Full DBT 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

DBT c.1281+5A>G Uncertain significance ★★ same condition
DBT p.Arg61Cys Uncertain significance ★★ ⚠ same condition
DBT p.Cys279Phe Uncertain significance ★★ ⚠ same condition
DBT p.Thr171Ile Uncertain significance ★★ ⚠ same condition
DBT p.Thr407Ala Uncertain significance ★★ ⚠ same condition
DBT p.Asn326= Likely benign ★★ same condition
DBT p.Ala458Val Uncertain significance ★ same condition
DBT p.Arg21His Conflicting classifications of pathogenicity ★ ⚠ 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/dbt-p-ile429ser (accessed [today's date]).

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