Is DHX38 p.Arg201Ter (c.601C>T) pathogenic?

DHX38 p.Arg201Ter (c.601C>T) is classified Likely pathogenic in DHX38 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). Very rare (popmax 0.000254%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with DHX38 p.Arg201Ter (c.601C>T)?

DHX38 p.Arg201Ter (c.601C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is DHX38 p.Arg201Ter (c.601C>T) in the general population?

DHX38 p.Arg201Ter (c.601C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

DHX38 p.Arg201Ter

c.601C>T · rs2144134187 · VCV3028418

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 27
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.68, phastCons 0.83
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,724 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,308 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)grpmax	0.000254%	393,241

Remaining individuals 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: DHX38
Protein: p.Arg201Ter
Coding: c.601C>T
MANE Select: NM_014003
dbSNP: rs2144134187
Type: single nucleotide variant
Location: chr16:72097766 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.82 · 5 PDB
Residue 201: the 'disordered' region

Full DHX38 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHX38 p.Arg201Gln Uncertain significance ★ ⚠ same residue
DHX38 c.2011-3C>A Uncertain significance ★★ same condition
DHX38 p.Ala113Val Uncertain significance ★★ ⚠ same condition
DHX38 p.Ala403Thr Uncertain significance ★★ ⚠ same condition
DHX38 p.Ala770Val Uncertain significance ★★ ⚠ same condition
DHX38 p.Arg1045Gln Uncertain significance ★★ ⚠ same condition
DHX38 p.Arg1162His Uncertain significance ★★ ⚠ same condition
DHX38 p.Arg1164Gln 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/dhx38-p-arg201ter (accessed [today's date]).

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