Is DNMBP p.Glu1575= (c.4725G>A) pathogenic?

DNMBP p.Glu1575= (c.4725G>A) is classified Benign in DNMBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-21). Low-frequency (popmax 2.58%, nfe); Associated with DNMBP-related disorder.

What condition is associated with DNMBP p.Glu1575= (c.4725G>A)?

DNMBP p.Glu1575= (c.4725G>A) is associated with DNMBP-related disorder (ClinVar).

How common is DNMBP p.Glu1575= (c.4725G>A) in the general population?

DNMBP p.Glu1575= (c.4725G>A) is low-frequency (popmax 2.58%, nfe) (gnomAD).

DNMBP p.Glu1575=

c.4725G>A · rs11190304 · VCV3038273

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.58%, nfe)

Conditions

DNMBP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -0.3, phastCons 0.88
Overall
CADD	8.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.58% European (non-Finnish) · 30,380/1,178,102 alleles

Filtering AF 2.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.54%

Overall 2.25% 36,284/1,609,802 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.82%	21
Finnishnot grpmax-eligible	3.39%	30
Ashkenazi Jewishnot grpmax-eligible	2.67%	37
European (non-Finnish)grpmax	2.58%	39
Remaining individualsnot grpmax-eligible	1.85%	54
Middle Eastern	1.09%	92
South Asian	0.942%	106
Admixed American	0.914%	109
African / African-American	0.389%	257
East Asian	0.0045%	22,245

Amish 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: DNMBP
Protein: p.Glu1575=
Coding: c.4725G>A
MANE Select: NM_015221
dbSNP: rs11190304
Type: single nucleotide variant
Location: chr10:99877160 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.91 · 7 PDB
Residue 1575: a UniProt-annotated variant site (in ctrct48); the sh3 6 domain

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

Disease context

DNMBP-related disorder

Similar variants

DNMBP c.2261-21460G>A Uncertain significance ★ same condition
DNMBP c.2261-20475C>G Benign same condition
DNMBP c.2261-20486G>A Benign same condition
DNMBP c.2261-20487C>T Benign same condition
DNMBP c.2261-20815A>G Benign same condition
DNMBP c.2261-21193G>A Benign same condition
DNMBP c.2261-21218G>A Benign same condition
DNMBP c.2261-21476T>C Benign same condition

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/dnmbp-p-glu1575 (accessed [today's date]).

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