Is DHX16 p.Arg199Pro (c.596G>C) pathogenic?

DHX16 p.Arg199Pro (c.596G>C) is classified Uncertain significance in DHX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely pathogenic (0.7002); Very rare (popmax 6.85e-05%); Associated with Inborn genetic diseases.

What condition is associated with DHX16 p.Arg199Pro (c.596G>C)?

DHX16 p.Arg199Pro (c.596G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DHX16 p.Arg199Pro (c.596G>C) in the general population?

DHX16 p.Arg199Pro (c.596G>C) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about DHX16 p.Arg199Pro (c.596G>C)?

AlphaMissense predicts likely pathogenic (score 0.7002) — an in-silico prediction, not a clinical call.

DHX16 p.Arg199Pro

c.596G>C · VCV3501536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7002 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7002	likely pathogenic
REVEL	0.216	benign-leaning
SaProt	LLR -7.86	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 7,978 bp · p 3.3e-05 · regional, not allelic
Overall
CADD	23.5	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 6.85e-05%

Overall 6.85e-05% 1/1,460,708 alleles · very rare

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: DHX16
Protein: p.Arg199Pro
Coding: c.596G>C
MANE Select: NM_003587
Type: single nucleotide variant
Location: chr6:30670803 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 12 PDB
Residue 199: the 'disordered' region

Full DHX16 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

DHX16 p.Arg199Trp Uncertain significance ★ ⚠ same residue
DHX16 p.Arg940Cys Uncertain significance ★★ ⚠ same condition
DHX16 p.Arg956Gln Uncertain significance ★★ ⚠ same condition
DHX16 p.Glu105Lys Uncertain significance ★★ ⚠ same condition
DHX16 p.Glu995Gly Uncertain significance ★★ ⚠ same condition
DHX16 p.Ala215Val Uncertain significance ★ ⚠ same condition
DHX16 p.Ala34Ser Uncertain significance ★ ⚠ same condition
DHX16 p.Ala379Ser 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/dhx16-p-arg199pro (accessed [today's date]).

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