Is DHX38 p.Pro777Ser (c.2329C>T) pathogenic?

DHX38 p.Pro777Ser (c.2329C>T) is classified Likely pathogenic in DHX38 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-23). AlphaMissense: likely pathogenic (0.9824); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with DHX38 p.Pro777Ser (c.2329C>T)?

DHX38 p.Pro777Ser (c.2329C>T) is associated with retinitis pigmentosa (ClinVar).

How common is DHX38 p.Pro777Ser (c.2329C>T) in the general population?

DHX38 p.Pro777Ser (c.2329C>T) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DHX38 p.Pro777Ser (c.2329C>T)?

AlphaMissense predicts likely pathogenic (score 0.9824) — an in-silico prediction, not a clinical call.

DHX38 p.Pro777Ser

c.2329C>T · rs1597445687 · VCV812307

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9824 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.9824	likely pathogenic ✓ concordant with ClinVar
REVEL	0.502	indeterminate
SaProt	LLR -14.61	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 6,952 bp · p 6.7e-11 · regional, not allelic
Overall
CADD	25.9	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

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: DHX38
Protein: p.Pro777Ser
Coding: c.2329C>T
MANE Select: NM_014003
dbSNP: rs1597445687
Type: single nucleotide variant
Location: chr16:72105298 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.82 · 5 PDB
Residue 777: the helicase c-terminal domain; a β-strand

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

DHX38 p.Pro777= Likely benign ★ same residue
DHX38 c.2011-3C>A Uncertain significance ★★ same type
DHX38 c.2262+3G>C Uncertain significance ★★ same type
DHX38 c.2262+4C>T Uncertain significance ★★ same type
DHX38 c.2262+5G>A Uncertain significance ★★ same type
DHX38 c.2964+3G>C Uncertain significance ★★ same type
DHX38 c.616+3A>G Uncertain significance ★★ same type
DHX38 c.764+2T>G Uncertain significance ★★ same type

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-pro777ser (accessed [today's date]).

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