Is DNMBP p.Ser1440= (c.4320C>T) pathogenic?

DNMBP p.Ser1440= (c.4320C>T) is classified Benign in DNMBP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-30). Common (popmax 54.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with cataract 48.

What condition is associated with DNMBP p.Ser1440= (c.4320C>T)?

DNMBP p.Ser1440= (c.4320C>T) is associated with cataract 48 (ClinVar).

DNMBP p.Ser1440=

Q: How common is DNMBP p.Ser1440= (c.4320C>T) in the general population?

DNMBP p.Ser1440= (c.4320C>T) is common (popmax 54.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4320C>T · rs2255901 · VCV1255519

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 54.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

cataract 48

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	0.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 54.3% African / African-American · 40,691/74,930 alleles

Filtering AF 53.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 53.7%

Overall 50.9% 821,332/1,613,852 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	56.9%	2
African / African-Americangrpmax	54.3%	2
Middle Eastern	53.3%	2
European (non-Finnish)	52.3%	2
Remaining individualsnot grpmax-eligible	50.5%	2
Ashkenazi Jewishnot grpmax-eligible	49.6%	2
South Asian	49.6%	2
Admixed American	48.6%	2
Finnishnot grpmax-eligible	42.6%	2
East Asian	25.7%	4

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.Ser1440=
Coding: c.4320C>T
MANE Select: NM_015221
dbSNP: rs2255901
Type: single nucleotide variant
Location: chr10:99880039 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.91 · 7 PDB
Residue 1440: 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

cataract 48 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNMBP c.3156+7A>G Benign ★★ same condition
DNMBP p.Asn961= Benign ★★ same condition
DNMBP p.Cys1413Trp Benign ★★ same condition
DNMBP p.Pro1248= Benign ★★ same condition
DNMBP p.Pro444= Benign ★★ same condition
DNMBP p.Arg271Ter Pathogenic ★ same condition
DNMBP p.Gly481fs Likely pathogenic ★ same condition
DNMBP p.Glu982_Asp983insTer Pathogenic 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-ser1440 (accessed [today's date]).

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