Is DNMBP p.Pro1248= (c.3744A>G) pathogenic?

DNMBP p.Pro1248= (c.3744A>G) is classified Benign in DNMBP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-30). Common (popmax 59.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with cataract 48.

What condition is associated with DNMBP p.Pro1248= (c.3744A>G)?

DNMBP p.Pro1248= (c.3744A>G) is associated with cataract 48 (ClinVar).

DNMBP p.Pro1248=

Q: How common is DNMBP p.Pro1248= (c.3744A>G) in the general population?

DNMBP p.Pro1248= (c.3744A>G) is common (popmax 59.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3744A>G · rs2490763 · VCV1255521

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 59.2%, 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; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3
Overall
CADD	0.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 59.2% African / African-American · 44,194/74,702 alleles

Filtering AF 58.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 58.5%

Overall 51.2% 815,989/1,594,246 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	59.2%	2
Amishnot grpmax-eligible	56.9%	2
Middle Eastern	53.6%	2
European (non-Finnish)	52.3%	2
Remaining individualsnot grpmax-eligible	50.9%	2
South Asian	50%	2
Ashkenazi Jewishnot grpmax-eligible	49.6%	2
Admixed American	48.7%	2
Finnishnot grpmax-eligible	42.6%	2
East Asian	25.9%	4

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.Pro1248=
Coding: c.3744A>G
MANE Select: NM_015221
dbSNP: rs2490763
Type: single nucleotide variant
Location: chr10:99885741 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.91 · 7 PDB
Residue 1248: 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.Pro444= Benign ★★ same condition
DNMBP p.Ser1440= 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-pro1248 (accessed [today's date]).

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