Is DHX36 p.Pro608Ser (c.1822C>T) pathogenic?

DHX36 p.Pro608Ser (c.1822C>T) is classified Uncertain significance in DHX36 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1528); Absent from gnomAD v4.1.

How common is DHX36 p.Pro608Ser (c.1822C>T) in the general population?

DHX36 p.Pro608Ser (c.1822C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHX36 p.Pro608Ser (c.1822C>T)?

AlphaMissense predicts likely benign (score 0.1528) — an in-silico prediction, not a clinical call.

DHX36 p.Pro608Ser

c.1822C>T · VCV4240316

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1528 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1528	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -8.68	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 10	GERP 2.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 24 kb · p 3.8e-09 · regional, not allelic
Overall
CADD	26.3	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

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: DHX36
Protein: p.Pro608Ser
Coding: c.1822C>T
MANE Select: NM_020865
Type: single nucleotide variant
Location: chr3:154289819 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.77 · 3 PDB
Residue 608: the 'reca-like domain 2' region; the helicase c-terminal domain

Full DHX36 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHX36 p.Pro608Ala Uncertain significance ★ ⚠ same residue
DHX36 p.Ala104Thr Uncertain significance ★ ⚠ same type
DHX36 p.Ala104Val Uncertain significance ★ ⚠ same type
DHX36 p.Ala437Thr Uncertain significance ★ ⚠ same type
DHX36 p.Ala437Val Uncertain significance ★ ⚠ same type
DHX36 p.Ala456Val Uncertain significance ★ ⚠ same type
DHX36 p.Ala490Gly Uncertain significance ★ ⚠ same type
DHX36 p.Ala743Ser 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/dhx36-p-pro608ser (accessed [today's date]).

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