Is DHX38 p.Pro197= (c.591C>T) pathogenic?

DHX38 p.Pro197= (c.591C>T) is classified Likely benign in DHX38 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-26). Ultra-rare (popmax 0.0165%, sas); Associated with inherited retinal dystrophy.

What condition is associated with DHX38 p.Pro197= (c.591C>T)?

DHX38 p.Pro197= (c.591C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is DHX38 p.Pro197= (c.591C>T) in the general population?

DHX38 p.Pro197= (c.591C>T) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

DHX38 p.Pro197=

c.591C>T · rs763901646 · VCV747753

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -5.3
Overall
CADD	0.352	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,026 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00304% 49/1,613,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,068
African / African-American	0.0107%	9,364
Admixed American	0.01%	9,995
Remaining individualsnot grpmax-eligible	0.0032%	31,234
European (non-Finnish)	0.00153%	65,548

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.Pro197=
Coding: c.591C>T
MANE Select: NM_014003
dbSNP: rs763901646
Type: single nucleotide variant
Location: chr16:72097756 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.82 · 5 PDB
Residue 197: 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.Pro197Leu 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-pro197 (accessed [today's date]).

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