Is DNMBP p.Arg271Gln (c.812G>A) pathogenic?

DNMBP p.Arg271Gln (c.812G>A) is classified Uncertain significance in DNMBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0687); Very rare (popmax 0.0011%, sas).

How common is DNMBP p.Arg271Gln (c.812G>A) in the general population?

DNMBP p.Arg271Gln (c.812G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DNMBP p.Arg271Gln (c.812G>A)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

DNMBP p.Arg271Gln

c.812G>A · VCV4832206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -7.82	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 -2.5	GERP -3.7
Regional constraint	o/e 0.75	unconstrained · MANE · 16 kb · p 1.4e-07 · regional, not allelic
Overall
CADD	13.53	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,058 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,530 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,058
European (non-Finnish)	0.000339%	294,930

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.Arg271Gln
Coding: c.812G>A
MANE Select: NM_015221
Type: single nucleotide variant
Location: chr10:99956662 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.91 · 7 PDB
Residue 271: a UniProt-annotated variant site (in ctrct48); a β-strand; the sh3 4 domain

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

Similar variants

DNMBP p.Arg271Ter Pathogenic ★ 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
DNMBP p.Asn961= 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-arg271gln (accessed [today's date]).

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