Is DBP p.Ala149Val (c.446C>T) pathogenic?

DBP p.Ala149Val (c.446C>T) is classified Uncertain significance in DBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely benign (0.0823); Ultra-rare (popmax 0.0119%, nfe).

How common is DBP p.Ala149Val (c.446C>T) in the general population?

DBP p.Ala149Val (c.446C>T) is ultra-rare (popmax 0.0119%, nfe) (gnomAD).

What do computational predictors say about DBP p.Ala149Val (c.446C>T)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

DBP p.Ala149Val

c.446C>T · rs1227457524 · VCV2594802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.22, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,402 bp · p 0.58 · regional, not allelic
Overall
CADD	19.35	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0119% European (non-Finnish) · 124/1,043,984 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00951%

Overall 0.00984% 130/1,321,384 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0119%	8,419
Remaining individualsnot grpmax-eligible	0.00804%	12,439
South Asian	0.00216%	46,350
African / African-American	0.00155%	64,598

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.Ala149Val
Coding: c.446C>T
MANE Select: NM_001352
dbSNP: rs1227457524
Type: single nucleotide variant
Location: chr19:48635684 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.35
Residue 149: 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.Ala171Ser Uncertain significance ★ ⚠ same type
DBP p.Ala324Thr Uncertain significance ★ ⚠ same type
DBP p.Ala96Ser Uncertain significance ★ ⚠ same type
DBP p.Ala96Thr 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-ala149val (accessed [today's date]).

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