Is DNMBP p.Gln1272Pro (c.3815A>C) pathogenic?

DNMBP p.Gln1272Pro (c.3815A>C) is classified Uncertain significance in DNMBP (ClinVar, Single submitter, 2 submitters; last evaluated 2022-09-27). AlphaMissense: likely benign (0.2688); Ultra-rare (popmax 0.01%, amr).

How common is DNMBP p.Gln1272Pro (c.3815A>C) in the general population?

DNMBP p.Gln1272Pro (c.3815A>C) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DNMBP p.Gln1272Pro (c.3815A>C)?

AlphaMissense predicts likely benign (score 0.2688) — an in-silico prediction, not a clinical call.

DNMBP p.Gln1272Pro

c.3815A>C · rs200569120 · VCV1050131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2688 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2688	likely benign
REVEL	0.483	indeterminate
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 79 kb · p 0.11 · regional, not allelic
Overall
CADD	26.0	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 0.01% Admixed American · 6/60,000 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00601% 97/1,613,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.206%	485
Remaining individualsnot grpmax-eligible	0.0208%	4,802
Admixed Americangrpmax	0.01%	10,000
European (non-Finnish)	0.00144%	69,402

Ashkenazi Jewish 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: DNMBP
Protein: p.Gln1272Pro
Coding: c.3815A>C
MANE Select: NM_015221
dbSNP: rs200569120
Type: single nucleotide variant
Location: chr10:99884193 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.91 · 7 PDB
Residue 1272: 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.Gln1272Arg Uncertain significance ★ ⚠ same residue
DNMBP p.Gln1272Ter Uncertain significance ★ same residue
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

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-gln1272pro (accessed [today's date]).

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