Is DNMBP p.Pro820Leu (c.2459C>T) pathogenic?

DNMBP p.Pro820Leu (c.2459C>T) is classified Benign in DNMBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). AlphaMissense: likely benign (0.1349); Low-frequency (popmax 1.31%, sas); Associated with DNMBP-related disorder.

What condition is associated with DNMBP p.Pro820Leu (c.2459C>T)?

DNMBP p.Pro820Leu (c.2459C>T) is associated with DNMBP-related disorder (ClinVar).

How common is DNMBP p.Pro820Leu (c.2459C>T) in the general population?

DNMBP p.Pro820Leu (c.2459C>T) is low-frequency (popmax 1.31%, sas) (gnomAD).

What do computational predictors say about DNMBP p.Pro820Leu (c.2459C>T)?

AlphaMissense predicts likely benign (score 0.1349) — an in-silico prediction, not a clinical call.

DNMBP p.Pro820Leu

c.2459C>T · rs114927649 · VCV3053441

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1349 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.31%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DNMBP-related disorder

Computational evidence

Protein change
AlphaMissense	0.1349	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -9.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 0.72, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 79 kb · p 0.11 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.31% South Asian · 1,193/90,938 alleles

Filtering AF 1.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.23%

Overall 0.305% 4,917/1,610,134 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.31%	76
Amishnot grpmax-eligible	0.548%	182
Admixed American	0.32%	312
Middle Eastern	0.281%	356
European (non-Finnish)	0.278%	359
Remaining individualsnot grpmax-eligible	0.269%	371
African / African-American	0.0708%	1,413
Finnishnot grpmax-eligible	0.0219%	4,564
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592

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.Pro820Leu
Coding: c.2459C>T
MANE Select: NM_015221
dbSNP: rs114927649
Type: single nucleotide variant
Location: chr10:99908090 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.91 · 7 PDB
Residue 820: a UniProt-annotated variant site (in ctrct48); the dh 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-pro820leu (accessed [today's date]).

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