Is DMBX1 p.Pro151Ala (c.451C>G) pathogenic?

DMBX1 p.Pro151Ala (c.451C>G) is classified Uncertain significance in DMBX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely benign (0.0473); Very rare (popmax 0.00127%, nfe).

How common is DMBX1 p.Pro151Ala (c.451C>G) in the general population?

DMBX1 p.Pro151Ala (c.451C>G) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about DMBX1 p.Pro151Ala (c.451C>G)?

AlphaMissense predicts likely benign (score 0.0473) — an in-silico prediction, not a clinical call.

DMBX1 p.Pro151Ala

c.451C>G · rs777493237 · VCV3083073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0473 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0473	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -6.19	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 0.38	GERP 0.23
Regional constraint	o/e 0.97	unconstrained · MANE · 1,541 bp · p 0.55 · regional, not allelic
Overall
CADD	3.068	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P156A vs ClinVar P151A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,179,982 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00116% 17/1,461,776 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)grpmax	0.00127%	78,665

Remaining individuals 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: DMBX1
Protein: p.Pro151Ala
Coding: c.451C>G
MANE Select: NM_172225
dbSNP: rs777493237
Type: single nucleotide variant
Location: chr1:46511052 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.71
Residue 151: the 'interaction with otx2 and is required for repressor activity' region; the 'disordered' region

Full DMBX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMBX1 c.155-10A>T Uncertain significance ★ ⚠ same type
DMBX1 p.Ala213Val Uncertain significance ★ ⚠ same type
DMBX1 p.Ala239Val Uncertain significance ★ ⚠ same type
DMBX1 p.Ala27Ser Uncertain significance ★ ⚠ same type
DMBX1 p.Ala291Thr Uncertain significance ★ ⚠ same type
DMBX1 p.Ala295Thr Uncertain significance ★ ⚠ same type
DMBX1 p.Ala367Ser Uncertain significance ★ same type
DMBX1 p.Ala367Thr Uncertain significance ★ ⚠ 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/dmbx1-p-pro151ala (accessed [today's date]).

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