Is DNMBP p.Val249= (c.747C>T) pathogenic?

DNMBP p.Val249= (c.747C>T) is classified Benign in DNMBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-01). Common (popmax 30.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with DNMBP-related disorder.

What condition is associated with DNMBP p.Val249= (c.747C>T)?

DNMBP p.Val249= (c.747C>T) is associated with DNMBP-related disorder (ClinVar).

DNMBP p.Val249=

Q: How common is DNMBP p.Val249= (c.747C>T) in the general population?

DNMBP p.Val249= (c.747C>T) is common (popmax 30.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.747C>T · rs3750715 · VCV3056139

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 30.3%, eas) — too common for a highly-penetrant pathogenic allele

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	GERP -3.4
Overall
CADD	0.449	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.3% East Asian · 13,564/44,826 alleles

Filtering AF 29.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.7%

Overall 2.12% 34,203/1,613,988 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	30.3%	3
Finnishnot grpmax-eligible	4.78%	21
Admixed American	4.74%	21
South Asian	4.51%	22
Remaining individualsnot grpmax-eligible	3.04%	33
African / African-American	0.964%	104
European (non-Finnish)	0.663%	151
Ashkenazi Jewishnot grpmax-eligible	0.547%	183
Middle Eastern	0.346%	289
Amishnot grpmax-eligible	0.11%	912

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.Val249=
Coding: c.747C>T
MANE Select: NM_015221
dbSNP: rs3750715
Type: single nucleotide variant
Location: chr10:99956727 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.91 · 7 PDB
Residue 249: a β-strand; the sh3 4 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-val249 (accessed [today's date]).

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