Is DBNDD2 p.Glu24Lys (c.70G>A) pathogenic?

DBNDD2 p.Glu24Lys (c.70G>A) is classified Uncertain significance in DBNDD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-24). AlphaMissense: likely pathogenic (0.8919); Very rare (popmax 0.0011%, sas).

How common is DBNDD2 p.Glu24Lys (c.70G>A) in the general population?

DBNDD2 p.Glu24Lys (c.70G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DBNDD2 p.Glu24Lys (c.70G>A)?

AlphaMissense predicts likely pathogenic (score 0.8919) — an in-silico prediction, not a clinical call.

DBNDD2 p.Glu24Lys

c.70G>A · VCV3838342

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8919	likely pathogenic · top 5% in DBNDD2
REVEL	0.607	indeterminate
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,669 bp · p 0.4 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E122K vs ClinVar E24K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,088 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,886 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,088
European (non-Finnish)	0.000169%	590,019

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.Glu24Lys
Coding: c.70G>A
MANE Select: NM_001048225
Type: single nucleotide variant
Location: chr20:45408537 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 60.09

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

Similar variants

DBNDD2 c.78G>T Uncertain significance ★ same type
DBNDD2 c.95C>A Uncertain significance ★ same type
DBNDD2 c.-146C>T Uncertain significance ★ same type
DBNDD2 c.-15C>A Uncertain significance ★ ⚠ same type
DBNDD2 c.-29G>T Uncertain significance ★ ⚠ same type
DBNDD2 c.-32C>T Uncertain significance ★ ⚠ same type
DBNDD2 c.-5C>A Uncertain significance ★ ⚠ same type
DBNDD2 c.-5C>T 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/dbndd2-p-glu24lys (accessed [today's date]).

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