Is DBP p.Arg188Trp (c.562C>T) pathogenic?

DBP p.Arg188Trp (c.562C>T) is classified Uncertain significance in DBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: ambiguous (0.5287); Very rare (popmax 0.00992%, nfe).

How common is DBP p.Arg188Trp (c.562C>T) in the general population?

DBP p.Arg188Trp (c.562C>T) is very rare (popmax 0.00992%, nfe) (gnomAD).

What do computational predictors say about DBP p.Arg188Trp (c.562C>T)?

AlphaMissense predicts ambiguous (score 0.5287) — an in-silico prediction, not a clinical call.

DBP p.Arg188Trp

c.562C>T · rs754211626 · VCV2377734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5287 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00992%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5287	ambiguous
REVEL	0.243	benign-leaning
SaProt	LLR -9.26	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 2,139 bp · p 0.042 · 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 0.00992% European (non-Finnish) · 117/1,180,000 alleles

Filtering AF 0.00842% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00787%

Overall 0.00756% 122/1,613,846 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00992%	10,085
East Asian	0.00668%	14,967
African / African-American	0.00133%	74,916
South Asian	0.0011%	91,084

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.Arg188Trp
Coding: c.562C>T
MANE Select: NM_001352
dbSNP: rs754211626
Type: single nucleotide variant
Location: chr19:48633644 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.35
Residue 188: the 'disordered' region

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

Similar variants

DBP p.Arg188Gln Uncertain significance ★ ⚠ same residue
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

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-arg188trp (accessed [today's date]).

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