Is DHX16 p.Arg736Ser (c.2206C>A) pathogenic?

DHX16 p.Arg736Ser (c.2206C>A) is classified Uncertain significance in DHX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely pathogenic (0.9984); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DHX16 p.Arg736Ser (c.2206C>A)?

DHX16 p.Arg736Ser (c.2206C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DHX16 p.Arg736Ser (c.2206C>A) in the general population?

DHX16 p.Arg736Ser (c.2206C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHX16 p.Arg736Ser (c.2206C>A)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

DHX16 p.Arg736Ser

c.2206C>A · VCV4011359

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9984 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic · top 1% in DHX16
REVEL	0.521	indeterminate
SaProt	LLR -16.10	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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 0.58	unconstrained · MANE · 8,647 bp · p 7.4e-23 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DHX16
Protein: p.Arg736Ser
Coding: c.2206C>A
MANE Select: NM_003587
Type: single nucleotide variant
Location: chr6:30656702 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 12 PDB
Residue 736: the helicase c-terminal domain; a β-strand

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.Arg736Cys 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-arg736ser (accessed [today's date]).

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