Is DDX17 p.Pro701= (c.2103G>A) pathogenic?

DDX17 p.Pro701= (c.2103G>A) is classified Benign in DDX17 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-21). Common (popmax 8.76%, afr) — too common for a highly-penetrant pathogenic allele.

DDX17 p.Pro701=

Q: How common is DDX17 p.Pro701= (c.2103G>A) in the general population?

DDX17 p.Pro701= (c.2103G>A) is common (popmax 8.76%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2103G>A · rs13996 · VCV777708

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.76%, afr) — too common for a highly-penetrant pathogenic allele

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 -10	GERP -4.5
Overall
CADD	0.245	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.76% African / African-American · 6,562/74,890 alleles

Filtering AF 8.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.51%

Overall 0.478% 7,710/1,613,852 alleles · common exomes 3,948/1,461,888 · genomes 3,762/151,964 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.76%	11
Admixed American	0.562%	178
Remaining individualsnot grpmax-eligible	0.555%	180
Middle Eastern	0.495%	202
East Asian	0.0535%	1,869
European (non-Finnish)	0.0335%	2,987
South Asian	0.0165%	6,071

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: DDX17
Protein: p.Pro701=
Coding: c.2103G>A
MANE Select: NM_006386
dbSNP: rs13996
Type: single nucleotide variant
Location: chr22:38486022 (GRCh38)
Gene constraint: LOEUF 0.252 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.88 · 5 PDB
Residue 701: the 'transactivation domain' region; the 'disordered' region

Full DDX17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX17 c.738+1G>A Pathogenic ★ same type
DDX17 p.Arg511His Likely pathogenic ★ same type
DDX17 p.Asn378Ser Likely pathogenic ★ ⚠ same type
DDX17 p.Thr523Ala Likely pathogenic ★ same type
DDX17 c.1447+4T>C Uncertain significance ★ same type
DDX17 c.1684+1G>A Uncertain significance ★ same type
DDX17 c.1684+3A>T Uncertain significance ★ same type
DDX17 p.Ala22Thr 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/ddx17-p-pro701 (accessed [today's date]).

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