Is DBX1 p.Ser246Cys (c.737C>G) pathogenic?

DBX1 p.Ser246Cys (c.737C>G) is classified Uncertain significance in DBX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.3297); Very rare (popmax 0.00446%, eas).

How common is DBX1 p.Ser246Cys (c.737C>G) in the general population?

DBX1 p.Ser246Cys (c.737C>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DBX1 p.Ser246Cys (c.737C>G)?

AlphaMissense predicts likely benign (score 0.3297) — an in-silico prediction, not a clinical call.

DBX1 p.Ser246Cys

c.737C>G · rs780340433 · VCV2542140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3297 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3297	likely benign
REVEL	0.569	indeterminate
SaProt	LLR -13.24	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
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 1.08	unconstrained · MANE · 4,107 bp · p 0.095 · regional, not allelic
Overall
CADD	32.0	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 · 2/44,874 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000342% 5/1,461,616 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,437
European (non-Finnish)	0.000254%	393,343

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: DBX1
Protein: p.Ser246Cys
Coding: c.737C>G
MANE Select: NM_001029865
dbSNP: rs780340433
Type: single nucleotide variant
Location: chr11:20156509 (GRCh38)
Gene constraint: LOEUF 0.98 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.03
Residue 246: the 'disordered' region

Full DBX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBX1 p.Ala127Pro Uncertain significance ★ ⚠ same type
DBX1 p.Ala127Val Uncertain significance ★ ⚠ same type
DBX1 p.Ala314Thr Uncertain significance ★ ⚠ same type
DBX1 p.Ala314Val Uncertain significance ★ ⚠ same type
DBX1 p.Arg211Leu Uncertain significance ★ ⚠ same type
DBX1 p.Arg237Trp Uncertain significance ★ ⚠ same type
DBX1 p.Arg49Pro Uncertain significance ★ ⚠ same type
DBX1 p.Arg56Ser 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/dbx1-p-ser246cys (accessed [today's date]).

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