Is DNMBP p.Asp547= (c.1641C>T) pathogenic?

DNMBP p.Asp547= (c.1641C>T) is classified Likely benign in DNMBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-04). Ultra-rare (popmax 0.0587%, afr); Associated with DNMBP-related disorder.

What condition is associated with DNMBP p.Asp547= (c.1641C>T)?

DNMBP p.Asp547= (c.1641C>T) is associated with DNMBP-related disorder (ClinVar).

How common is DNMBP p.Asp547= (c.1641C>T) in the general population?

DNMBP p.Asp547= (c.1641C>T) is ultra-rare (popmax 0.0587%, afr) (gnomAD).

DNMBP p.Asp547=

c.1641C>T · rs371385100 · VCV3046112

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0587%, afr)

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 2.8	GERP -2.2, phastCons 1
Overall
CADD	2.619	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0587% African / African-American · 44/74,942 alleles

Filtering AF 0.0449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0401%

Overall 0.00297% 48/1,614,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0587%	1,703
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)	0.000169%	590,023

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.Asp547=
Coding: c.1641C>T
MANE Select: NM_015221
dbSNP: rs371385100
Type: single nucleotide variant
Location: chr10:99955833 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.91 · 7 PDB
Residue 547: a UniProt-annotated variant site (in ctrct48)

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-asp547 (accessed [today's date]).

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