Is DHX30 p.Phe614Ser (c.1841T>C) pathogenic?

DHX30 p.Phe614Ser (c.1841T>C) is classified Likely benign in DHX30 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: likely pathogenic (0.8867); Ultra-rare (popmax 0.0549%, sas); Associated with Inborn genetic diseases.

What condition is associated with DHX30 p.Phe614Ser (c.1841T>C)?

DHX30 p.Phe614Ser (c.1841T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DHX30 p.Phe614Ser (c.1841T>C) in the general population?

DHX30 p.Phe614Ser (c.1841T>C) is ultra-rare (popmax 0.0549%, sas) (gnomAD).

What do computational predictors say about DHX30 p.Phe614Ser (c.1841T>C)?

AlphaMissense predicts likely pathogenic (score 0.8867) — an in-silico prediction, not a clinical call.

DHX30 p.Phe614Ser

c.1841T>C · rs761825968 · VCV2407631

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8867 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8867	likely pathogenic
REVEL	0.229	benign-leaning
SaProt	LLR -9.12	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.81, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 504 bp · p 9.8e-06 · regional, not allelic
Overall
CADD	27.2	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 0.0549% South Asian · 50/91,082 alleles

Filtering AF 0.0427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0385%

Overall 0.0031% 50/1,613,376 alleles · ultra-rare

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: DHX30
Protein: p.Phe614Ser
Coding: c.1841T>C
MANE Select: NM_138615
dbSNP: rs761825968
Type: single nucleotide variant
Location: chr3:47846913 (GRCh38)
Gene constraint: LOEUF 0.08 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.09 · 1 PDB

Full DHX30 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHX30 p.Arg1180Gln Uncertain significance ★★ ⚠ same condition
DHX30 p.Arg412Cys Uncertain significance ★★ ⚠ same condition
DHX30 p.Arg598Cys Uncertain significance ★★ ⚠ same condition
DHX30 p.Asn445Ser Uncertain significance ★★ ⚠ same condition
DHX30 p.Cys1183Ser Uncertain significance ★★ ⚠ same condition
DHX30 p.Glu228Gly Uncertain significance ★★ ⚠ same condition
DHX30 p.Leu650Phe Uncertain significance ★★ ⚠ same condition
DHX30 p.Pro392Leu 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/dhx30-p-phe614ser (accessed [today's date]).

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