Is DNMBP p.Pro1463Leu (c.4388C>T) pathogenic?

DNMBP p.Pro1463Leu (c.4388C>T) is classified Likely benign in DNMBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.0672); Ultra-rare (popmax 0.0668%, eas).

How common is DNMBP p.Pro1463Leu (c.4388C>T) in the general population?

DNMBP p.Pro1463Leu (c.4388C>T) is ultra-rare (popmax 0.0668%, eas) (gnomAD).

What do computational predictors say about DNMBP p.Pro1463Leu (c.4388C>T)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

DNMBP p.Pro1463Leu

c.4388C>T · rs116424120 · VCV2598872

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.35	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 -2.4	GERP -2.8
Regional constraint	o/e 0.96	unconstrained · MANE · 79 kb · p 0.11 · regional, not allelic
Overall
CADD	0.015	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 0.0668% East Asian · 30/44,906 alleles

Filtering AF 0.0481% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0417%

Overall 0.00366% 59/1,614,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0668%	1,497
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00212%	47,202
Admixed American	0.00167%	60,002
South Asian	0.0011%	91,090

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.Pro1463Leu
Coding: c.4388C>T
MANE Select: NM_015221
dbSNP: rs116424120
Type: single nucleotide variant
Location: chr10:99879971 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.91 · 7 PDB
Residue 1463: the 'disordered' region; a UniProt-annotated variant site (in ctrct48)

Full DNMBP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNMBP p.Arg1326His Uncertain significance ★★ ⚠ same type
DNMBP p.Asn1560Lys Uncertain significance ★★ ⚠ same type
DNMBP p.Ser984Cys Uncertain significance ★★ ⚠ same type
DNMBP c.2554+8C>T Benign/Likely benign ★★ same type
DNMBP c.3156+7A>G Benign ★★ same type
DNMBP p.Asn373Lys Benign ★★ same type
DNMBP p.Asn961= Benign ★★ same type
DNMBP p.Cys1413Trp Benign ★★ same type

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-pro1463leu (accessed [today's date]).

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