Is DBP p.Pro142Leu (c.425C>T) pathogenic?

DBP p.Pro142Leu (c.425C>T) is classified Uncertain significance in DBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.0992); Very rare (popmax 0.00309%, afr).

How common is DBP p.Pro142Leu (c.425C>T) in the general population?

DBP p.Pro142Leu (c.425C>T) is very rare (popmax 0.00309%, afr) (gnomAD).

What do computational predictors say about DBP p.Pro142Leu (c.425C>T)?

AlphaMissense predicts likely benign (score 0.0992) — an in-silico prediction, not a clinical call.

DBP p.Pro142Leu

c.425C>T · rs895951153 · VCV3080206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00309%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0992	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -8.32	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 5.5	GERP -2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,402 bp · p 0.58 · regional, not allelic
Overall
CADD	21.7	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 0.00309% African / African-American · 2/64,738 alleles

Filtering AF 0.000513% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000192%

Overall 0.000452% 6/1,326,626 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00522%	19,168
Remaining individualsnot grpmax-eligible	0.004%	25,008
African / African-Americangrpmax	0.00309%	32,369
European (non-Finnish)	9.55e-05%	1,046,750

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro142Leu
Coding: c.425C>T
MANE Select: NM_001352
dbSNP: rs895951153
Type: single nucleotide variant
Location: chr19:48635705 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.35
Residue 142: 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-pro142leu (accessed [today's date]).

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