Is DHX29 p.Leu847Pro (c.2540T>C) pathogenic?

DHX29 p.Leu847Pro (c.2540T>C) is classified Uncertain significance in DHX29 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely benign (0.2961); Very rare (popmax 0.000848%, nfe).

How common is DHX29 p.Leu847Pro (c.2540T>C) in the general population?

DHX29 p.Leu847Pro (c.2540T>C) is very rare (popmax 0.000848%, nfe) (gnomAD).

What do computational predictors say about DHX29 p.Leu847Pro (c.2540T>C)?

AlphaMissense predicts likely benign (score 0.2961) — an in-silico prediction, not a clinical call.

DHX29 p.Leu847Pro

c.2540T>C · rs975763510 · VCV2399675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2961	likely benign
REVEL	0.332	indeterminate
SaProt	LLR -14.51	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 1.1e-09 · regional, not allelic
Overall
CADD	26.5	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 0.000848% European (non-Finnish) · 10/1,179,882 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000684% 10/1,461,360 alleles · very 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: DHX29
Protein: p.Leu847Pro
Coding: c.2540T>C
dbSNP: rs975763510
Type: single nucleotide variant
Location: chr5:55274898 (GRCh38)

Full DHX29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dhx29-p-leu847pro (accessed [today's date]).

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