Is DBP p.Cys47Tyr (c.140G>A) pathogenic?

DBP p.Cys47Tyr (c.140G>A) is classified Uncertain significance in DBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: ambiguous (0.4218); Very rare (popmax 0.00606%, amr).

How common is DBP p.Cys47Tyr (c.140G>A) in the general population?

DBP p.Cys47Tyr (c.140G>A) is very rare (popmax 0.00606%, amr) (gnomAD).

What do computational predictors say about DBP p.Cys47Tyr (c.140G>A)?

AlphaMissense predicts ambiguous (score 0.4218) — an in-silico prediction, not a clinical call.

DBP p.Cys47Tyr

c.140G>A · rs759423285 · VCV2214825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4218 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00606%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4218	ambiguous
REVEL	0.097	moderately benign-leaning
SaProt	LLR -7.08	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.46 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.4	GERP 1.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,402 bp · p 0.58 · regional, not allelic
Overall
CADD	23.5	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 0.00606% Admixed American · 3/49,486 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000846%

Overall 0.000859% 13/1,512,544 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00606%	16,495
European (non-Finnish)	0.00088%	113,662

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: DBP
Protein: p.Cys47Tyr
Coding: c.140G>A
MANE Select: NM_001352
dbSNP: rs759423285
Type: single nucleotide variant
Location: chr19:48635990 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.35
Residue 47: the 'disordered' region

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

Similar variants

DBP p.Gly24Ser Likely benign ★★ same type
DBP p.Pro250= Likely benign ★★ same type
DBP p.Ser156= Likely benign ★★ same type
DBP p.Val304= Benign ★★ same type
DBP p.Ala149Val Uncertain significance ★ ⚠ same type
DBP p.Ala171Ser Uncertain significance ★ ⚠ same type
DBP p.Ala324Thr Uncertain significance ★ ⚠ same type
DBP p.Ala96Ser 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/dbp-p-cys47tyr (accessed [today's date]).

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