Is DDX49 p.Val57= (c.171C>T) pathogenic?

DDX49 p.Val57= (c.171C>T) is classified Likely benign in DDX49 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). Rare (popmax 0.252%, nfe).

How common is DDX49 p.Val57= (c.171C>T) in the general population?

DDX49 p.Val57= (c.171C>T) is rare (popmax 0.252%, nfe) (gnomAD).

DDX49 p.Val57=

c.171C>T · rs34332105 · VCV2649602

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.252%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.7	GERP -2.9, phastCons 0.001
Overall
CADD	10.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.252% European (non-Finnish) · 2,968/1,178,124 alleles

Filtering AF 0.244% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.241%

Overall 0.222% 3,575/1,611,850 alleles · rare exomes 3,343/1,459,552 · genomes 232/152,298 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.335%	299
Finnishnot grpmax-eligible	0.255%	393
European (non-Finnish)grpmax	0.252%	397
Remaining individualsnot grpmax-eligible	0.224%	446
South Asian	0.155%	645
Admixed American	0.055%	1,817
African / African-American	0.04%	2,501
Middle Eastern	0.0165%	6,052

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DDX49
Protein: p.Val57=
Coding: c.171C>T
MANE Select: NM_019070
dbSNP: rs34332105
Type: single nucleotide variant
Location: chr19:18920635 (GRCh38)
Gene constraint: LOEUF 1.194 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.72
Residue 57: the helicase atp-binding domain

Full DDX49 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX49 p.Val57Leu Uncertain significance ★ same residue
DDX49 p.Ala132Val Uncertain significance ★ ⚠ same type
DDX49 p.Ala154Val Uncertain significance ★ ⚠ same type
DDX49 p.Ala174Glu Uncertain significance ★ ⚠ same type
DDX49 p.Ala174Val Uncertain significance ★ ⚠ same type
DDX49 p.Ala233Pro Uncertain significance ★ ⚠ same type
DDX49 p.Ala290Thr Uncertain significance ★ ⚠ same type
DDX49 p.Ala35Pro 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/ddx49-p-val57 (accessed [today's date]).

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