Is DHX38 p.Val348Met (c.1042G>A) pathogenic?

DHX38 p.Val348Met (c.1042G>A) is classified Uncertain significance in DHX38 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-06). AlphaMissense: likely benign (0.2944); Very rare (popmax 0.00891%, eas).

How common is DHX38 p.Val348Met (c.1042G>A) in the general population?

DHX38 p.Val348Met (c.1042G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DHX38 p.Val348Met (c.1042G>A)?

AlphaMissense predicts likely benign (score 0.2944) — an in-silico prediction, not a clinical call.

DHX38 p.Val348Met

c.1042G>A · rs201188851 · VCV808075

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2944 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2944	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -4.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 1,304 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00123% 18/1,461,728 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
Remaining individualsnot grpmax-eligible	0.0032%	31,249
European (non-Finnish)	0.00102%	98,330

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.Val348Met
Coding: c.1042G>A
MANE Select: NM_014003
dbSNP: rs201188851
Type: single nucleotide variant
Location: chr16:72099813 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.82 · 5 PDB

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

Similar variants

DHX38 p.Val348= Benign/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-val348met (accessed [today's date]).

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