Is DNMBP p.Ser1478= (c.4434C>T) pathogenic?

DNMBP p.Ser1478= (c.4434C>T) is classified Benign in DNMBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-05). Common (popmax 8.85%, sas) — too common for a highly-penetrant pathogenic allele; Associated with DNMBP-related disorder.

What condition is associated with DNMBP p.Ser1478= (c.4434C>T)?

DNMBP p.Ser1478= (c.4434C>T) is associated with DNMBP-related disorder (ClinVar).

DNMBP p.Ser1478=

Q: How common is DNMBP p.Ser1478= (c.4434C>T) in the general population?

DNMBP p.Ser1478= (c.4434C>T) is common (popmax 8.85%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4434C>T · rs61757225 · VCV3060443

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 8.85%, sas) — 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 -0.88	GERP -3
Overall
CADD	1.581	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.85% South Asian · 8,062/91,084 alleles

Filtering AF 8.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.62%

Overall 3.63% 58,668/1,614,182 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	8.85%	11
European (non-Finnish)	3.62%	28
Remaining individualsnot grpmax-eligible	3.55%	28
African / African-American	2.65%	38
Finnishnot grpmax-eligible	2.61%	38
Middle Eastern	2.38%	42
Ashkenazi Jewishnot grpmax-eligible	2.36%	42
Amishnot grpmax-eligible	1.97%	51
Admixed American	1.92%	52
East Asian	0.0757%	1,320

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.Ser1478=
Coding: c.4434C>T
MANE Select: NM_015221
dbSNP: rs61757225
Type: single nucleotide variant
Location: chr10:99879925 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.91 · 7 PDB
Residue 1478: the 'disordered' region; 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-ser1478 (accessed [today's date]).

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