Is DHX29 p.Ala10Pro (c.28G>C) pathogenic?

DHX29 p.Ala10Pro (c.28G>C) is classified Uncertain significance in DHX29 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely benign (0.0966); Ultra-rare (popmax 0.0667%, amr).

How common is DHX29 p.Ala10Pro (c.28G>C) in the general population?

DHX29 p.Ala10Pro (c.28G>C) is ultra-rare (popmax 0.0667%, amr) (gnomAD).

What do computational predictors say about DHX29 p.Ala10Pro (c.28G>C)?

AlphaMissense predicts likely benign (score 0.0966) — an in-silico prediction, not a clinical call.

DHX29 p.Ala10Pro

c.28G>C · rs746968420 · VCV2391069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0966 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0966	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -6.60	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 0.82	GERP -2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 22 kb · p 0.56 · regional, not allelic
Overall
CADD	16.84	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 0.0667% Admixed American · 40/60,008 alleles

Filtering AF 0.0503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0446%

Overall 0.00304% 49/1,613,600 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0667%	1,500
Remaining individualsnot grpmax-eligible	0.00801%	12,490
European (non-Finnish)	0.000339%	294,991

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.Ala10Pro
Coding: c.28G>C
MANE Select: NM_019030
dbSNP: rs746968420
Type: single nucleotide variant
Location: chr5:55307546 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.75 · 2 PDB

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

Similar variants

DHX29 p.Thr47Ala Uncertain significance ★★ ⚠ same type
DHX29 p.Ala158Thr Uncertain significance ★ ⚠ same type
DHX29 p.Ala33Pro Uncertain significance ★ ⚠ same type
DHX29 p.Ala53Thr Uncertain significance ★ ⚠ same type
DHX29 p.Arg24Thr Uncertain significance ★ ⚠ same type
DHX29 p.Arg97Ile Uncertain significance ★ ⚠ same type
DHX29 p.Asn110Ser Uncertain significance ★ ⚠ same type
DHX29 p.Asn228Thr 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/dhx29-p-ala10pro (accessed [today's date]).

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