Is DDX41 p.Lys115Arg (c.344A>G) pathogenic?

DDX41 p.Lys115Arg (c.344A>G) is classified Likely benign in DDX41 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-11). AlphaMissense: likely benign (0.115); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with DDX41 p.Lys115Arg (c.344A>G)?

DDX41 p.Lys115Arg (c.344A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DDX41 p.Lys115Arg (c.344A>G) in the general population?

DDX41 p.Lys115Arg (c.344A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DDX41 p.Lys115Arg (c.344A>G)?

AlphaMissense predicts likely benign (score 0.115) — an in-silico prediction, not a clinical call.

DDX41 p.Lys115Arg

c.344A>G · VCV4844601

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.115 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.115	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 369 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	24.7	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 0.0011% South Asian · 1/91,086 alleles

Overall 0.000124% 2/1,614,072 alleles · very rare exomes 2/1,461,720 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,086
European (non-Finnish)	8.47e-05%	1,180,043

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: DDX41
Protein: p.Lys115Arg
Coding: c.344A>G
MANE Select: NM_016222
Type: single nucleotide variant
Location: chr5:177516148 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 115: a cross-link site

Full DDX41 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DDX41 p.Lys115= Likely benign ★ same residue
DDX41 c.1303-2A>G Likely pathogenic ★★ same condition
DDX41 c.27+1G>A Likely pathogenic ★★ same condition
DDX41 c.434+1G>C Pathogenic/Likely pathogenic ★★ same condition
DDX41 c.571+1G>A Likely pathogenic ★★ same condition
DDX41 c.572-1G>A Pathogenic/Likely pathogenic ★★ same condition
DDX41 p.Arg159Ter Pathogenic ★★ same condition
DDX41 p.Arg369Ter Pathogenic/Likely pathogenic ★★ 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/ddx41-p-lys115arg (accessed [today's date]).

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