Is DBNDD2 p.His39Asp (c.115C>G) pathogenic?

DBNDD2 p.His39Asp (c.115C>G) is classified Uncertain significance in DBNDD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.2834); Rare (popmax 0.282%, amr).

How common is DBNDD2 p.His39Asp (c.115C>G) in the general population?

DBNDD2 p.His39Asp (c.115C>G) is rare (popmax 0.282%, amr) (gnomAD).

What do computational predictors say about DBNDD2 p.His39Asp (c.115C>G)?

AlphaMissense predicts likely benign (score 0.2834) — an in-silico prediction, not a clinical call.

DBNDD2 p.His39Asp

c.115C>G · rs774496791 · VCV2389884

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2834 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.282%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2834	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP 1.8, phastCons 1
Overall
CADD	21.2	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 0.282% Admixed American · 126/44,704 alleles

Filtering AF 0.242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.227%

Overall 0.0107% 159/1,489,658 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.282%	355
Ashkenazi Jewishnot grpmax-eligible	0.0506%	1,978
Remaining individualsnot grpmax-eligible	0.0192%	5,210
African / African-American	0.00146%	68,412
European (non-Finnish)	0.000716%	139,677

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: DBNDD2
Protein: p.His39Asp
Coding: c.115C>G
dbSNP: rs774496791
Type: single nucleotide variant
Location: chr20:45406566 (GRCh38)

Full DBNDD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dbndd2-p-his39asp (accessed [today's date]).

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