Is DHX38 p.Leu764Val (c.2290C>G) pathogenic?

DHX38 p.Leu764Val (c.2290C>G) is classified Uncertain significance in DHX38 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). AlphaMissense: ambiguous (0.3868); Very rare (popmax 0.00167%, amr).

How common is DHX38 p.Leu764Val (c.2290C>G) in the general population?

DHX38 p.Leu764Val (c.2290C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DHX38 p.Leu764Val (c.2290C>G)?

AlphaMissense predicts ambiguous (score 0.3868) — an in-silico prediction, not a clinical call.

DHX38 p.Leu764Val

c.2290C>G · rs2042158932 · VCV1963754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3868 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3868	ambiguous
REVEL	0.136	moderately benign-leaning
SaProt	LLR -7.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.44, phastCons 0.99
Regional constraint	o/e 0.76	unconstrained · MANE · 6,952 bp · p 6.7e-11 · regional, not allelic
Overall
CADD	21.6	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 0.00167% Admixed American · 1/60,008 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,070 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,008
European (non-Finnish)	0.000169%	590,023

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.Leu764Val
Coding: c.2290C>G
MANE Select: NM_014003
dbSNP: rs2042158932
Type: single nucleotide variant
Location: chr16:72105259 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.82 · 5 PDB
Residue 764: the helicase c-terminal domain; an α-helix

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

Similar variants

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
DHX38 p.Ala113Val 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-leu764val (accessed [today's date]).

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