Is DNMBP p.Ala152Val (c.455C>T) pathogenic?

DNMBP p.Ala152Val (c.455C>T) is classified Uncertain significance in DNMBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely pathogenic (0.8153); Very rare (popmax 0.00864%, nfe).

How common is DNMBP p.Ala152Val (c.455C>T) in the general population?

DNMBP p.Ala152Val (c.455C>T) is very rare (popmax 0.00864%, nfe) (gnomAD).

What do computational predictors say about DNMBP p.Ala152Val (c.455C>T)?

AlphaMissense predicts likely pathogenic (score 0.8153) — an in-silico prediction, not a clinical call.

DNMBP p.Ala152Val

c.455C>T · VCV4243548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00864%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8153	likely pathogenic
REVEL	0.361	indeterminate
SaProt	LLR -12.19	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 16 kb · p 1.4e-07 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00864% European (non-Finnish) · 102/1,180,042 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00676%

Overall 0.00644% 104/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00864%	11,569
African / African-American	0.00267%	37,464

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.Ala152Val
Coding: c.455C>T
Type: single nucleotide variant
Location: chr10:99957019 (GRCh38)

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

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-ala152val (accessed [today's date]).

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