Is DDX59 p.Ser477= (c.1431A>G) pathogenic?

DDX59 p.Ser477= (c.1431A>G) is classified Benign in DDX59 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with orofaciodigital syndrome V.

What condition is associated with DDX59 p.Ser477= (c.1431A>G)?

DDX59 p.Ser477= (c.1431A>G) is associated with orofaciodigital syndrome V (ClinVar).

DDX59 p.Ser477=

Q: How common is DDX59 p.Ser477= (c.1431A>G) in the general population?

DDX59 p.Ser477= (c.1431A>G) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1431A>G · rs6665604 · VCV1255474

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

orofaciodigital syndrome V

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.096	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -4.8
Overall
CADD	0.041	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 43,564/43,568 alleles

Filtering AF 99.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.9%

Overall 96.3% 1,508,428/1,566,354 alleles · common exomes 1,363,194/1,414,098 · genomes 145,234/152,256 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
Finnishnot grpmax-eligible	98.8%	1
South Asian	97.8%	1
Admixed American	96.7%	1
Remaining individualsnot grpmax-eligible	96.4%	1
European (non-Finnish)	96.2%	1
Ashkenazi Jewishnot grpmax-eligible	95.9%	1
Amishnot grpmax-eligible	95.4%	1
Middle Eastern	94.5%	1
African / African-American	92.4%	1

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: DDX59
Protein: p.Ser477=
Coding: c.1431A>G
MANE Select: NM_001031725
dbSNP: rs6665604
Type: single nucleotide variant
Location: chr1:200649110 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.71 · 1 PDB
Residue 477: the helicase c-terminal domain

Full DDX59 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

orofaciodigital syndrome V — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DDX59 p.Val367Gly Pathogenic/Likely pathogenic ★★ same condition
DDX59 p.His171Tyr Uncertain significance ★★ ⚠ same condition
DDX59 p.Ile9Met Uncertain significance ★★ ⚠ same condition
DDX59 c.1314+23A>G Benign ★★ same condition
DDX59 c.1597-6T>G Likely pathogenic ★ same condition
DDX59 p.Ter620Leu Pathogenic ★ same condition
DDX59 p.Gly534Arg Uncertain significance ★ ⚠ same condition
DDX59 p.Ser251Pro Uncertain significance ★ ⚠ same condition

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/ddx59-p-ser477 (accessed [today's date]).

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