Is DDX51 p.Arg366Cys (c.1096C>T) pathogenic?

DDX51 p.Arg366Cys (c.1096C>T) is classified Uncertain significance in DDX51 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely benign (0.1989); Very rare (popmax 0.00805%, afr).

How common is DDX51 p.Arg366Cys (c.1096C>T) in the general population?

DDX51 p.Arg366Cys (c.1096C>T) is very rare (popmax 0.00805%, afr) (gnomAD).

What do computational predictors say about DDX51 p.Arg366Cys (c.1096C>T)?

AlphaMissense predicts likely benign (score 0.1989) — an in-silico prediction, not a clinical call.

DDX51 p.Arg366Cys

c.1096C>T · rs748206872 · VCV2206588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00805%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1989	likely benign
REVEL	0.454	indeterminate
SaProt	LLR -10.01	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 12	GERP 1.3, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 5,021 bp · p 5.4e-07 · 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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00805% African / African-American · 6/74,558 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00277%

Overall 0.00346% 55/1,591,654 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00805%	12,426
European (non-Finnish)	0.00401%	24,933
East Asian	0.00224%	44,624
Remaining individualsnot grpmax-eligible	0.00162%	61,730

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: DDX51
Protein: p.Arg366Cys
Coding: c.1096C>T
MANE Select: NM_175066
dbSNP: rs748206872
Type: single nucleotide variant
Location: chr12:132141506 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.64
Residue 366: the helicase atp-binding domain

Full DDX51 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX51 p.Gly542= Likely benign ★★ same type
DDX51 p.Ala107Ser Uncertain significance ★ ⚠ same type
DDX51 p.Ala119Val Uncertain significance ★ ⚠ same type
DDX51 p.Ala141Thr Uncertain significance ★ ⚠ same type
DDX51 p.Ala144Thr Uncertain significance ★ ⚠ same type
DDX51 p.Ala183Pro Uncertain significance ★ ⚠ same type
DDX51 p.Ala237Pro Uncertain significance ★ ⚠ same type
DDX51 p.Ala25Thr 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/ddx51-p-arg366cys (accessed [today's date]).

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