Is DDX27 p.Arg306Gln (c.917G>A) pathogenic?

DDX27 p.Arg306Gln (c.917G>A) is classified Uncertain significance in DDX27 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: ambiguous (0.5441); Very rare (popmax 0.00133%, afr).

How common is DDX27 p.Arg306Gln (c.917G>A) in the general population?

DDX27 p.Arg306Gln (c.917G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DDX27 p.Arg306Gln (c.917G>A)?

AlphaMissense predicts ambiguous (score 0.5441) — an in-silico prediction, not a clinical call.

DDX27 p.Arg306Gln

c.917G>A · VCV3838879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5441 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.5441	ambiguous
REVEL	0.478	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 9e-11 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R337Q vs ClinVar R306Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,030 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000342% 5/1,460,858 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,030
South Asian	0.0011%	91,072
European (non-Finnish)	0.000254%	393,317

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: DDX27
Protein: p.Arg306Gln
Coding: c.917G>A
MANE Select: NM_017895
Type: single nucleotide variant
Location: chr20:49230235 (GRCh38)
Gene constraint: LOEUF 0.528 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 72.06
Residue 306: the helicase atp-binding domain

Full DDX27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX27 p.Ala239= Benign ★★ same type
DDX27 p.Glu172Lys Benign ★★ same type
DDX27 c.52C>G Uncertain significance ★ same type
DDX27 c.-33G>A Uncertain significance ★ ⚠ same type
DDX27 p.Ala147Thr Uncertain significance ★ ⚠ same type
DDX27 p.Ala256Thr Uncertain significance ★ ⚠ same type
DDX27 p.Ala308Val Uncertain significance ★ ⚠ same type
DDX27 p.Ala553Val 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/ddx27-p-arg306gln (accessed [today's date]).

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