Is DBP p.Ile240Val (c.718A>G) pathogenic?

DBP p.Ile240Val (c.718A>G) is classified Uncertain significance in DBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely pathogenic (0.6416); Very rare (popmax 0.00439%, sas).

How common is DBP p.Ile240Val (c.718A>G) in the general population?

DBP p.Ile240Val (c.718A>G) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about DBP p.Ile240Val (c.718A>G)?

AlphaMissense predicts likely pathogenic (score 0.6416) — an in-silico prediction, not a clinical call.

DBP p.Ile240Val

c.718A>G · VCV3499797

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6416 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6416	likely pathogenic
REVEL	0.169	moderately benign-leaning
SaProt	LLR -9.07	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 2,139 bp · p 0.042 · regional, not allelic
Overall
CADD	25.7	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 0.00439% South Asian · 4/91,090 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000372% 6/1,614,092 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,773
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Ile240Val
Coding: c.718A>G
MANE Select: NM_001352
Type: single nucleotide variant
Location: chr19:48633488 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.35
Residue 240: 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-ile240val (accessed [today's date]).

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