Is DDX3X p.Ser606= (c.1818C>T) pathogenic?

DDX3X p.Ser606= (c.1818C>T) is classified Likely benign in DDX3X (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-17). Very rare (popmax 0.00313%, nfe).

How common is DDX3X p.Ser606= (c.1818C>T) in the general population?

DDX3X p.Ser606= (c.1818C>T) is very rare (popmax 0.00313%, nfe) (gnomAD).

DDX3X p.Ser606=

c.1818C>T · rs1291725741 · VCV1897984

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00313%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.9	GERP -4.8
Overall
CADD	0.505	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00313% European (non-Finnish) · 28/894,893 alleles

Filtering AF 0.00217% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00187%

Overall 0.00265% 32/1,209,571 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00313%	31,960
Finnishnot grpmax-eligible	0.00215%	46,538
Remaining individualsnot grpmax-eligible	0.0021%	47,586
South Asian	0.00176%	56,813
African / African-American	0.00175%	57,175

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: DDX3X
Protein: p.Ser606=
Coding: c.1818C>T
MANE Select: NM_001356
dbSNP: rs1291725741
Type: single nucleotide variant
Location: chrX:41347360 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 606: the 'interaction with hcv core protein' region; the 'interaction with nxf1' region; the 'disordered' region; the 'interaction with gsk3b' region

Full DDX3X gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX3X p.Ser606del Conflicting classifications of pathogenicity ★ same residue
DDX3X c.1497+1G>A Likely pathogenic ★★ same type
DDX3X c.1498-2A>G Pathogenic ★★ same type
DDX3X c.151+1G>A Pathogenic ★★ same type
DDX3X c.1769+1G>A Pathogenic ★★ same type
DDX3X c.765+1G>A Pathogenic ★★ same type
DDX3X c.865-1G>A Pathogenic ★★ same type
DDX3X c.865-1G>C Pathogenic ★★ 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/ddx3x-p-ser606 (accessed [today's date]).

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