Is DHX32 p.Ala529Ser (c.1585G>T) pathogenic?

DHX32 p.Ala529Ser (c.1585G>T) is classified Uncertain significance in DHX32 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-16). AlphaMissense: likely benign (0.0922); Very rare (popmax 0.00935%, afr).

How common is DHX32 p.Ala529Ser (c.1585G>T) in the general population?

DHX32 p.Ala529Ser (c.1585G>T) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about DHX32 p.Ala529Ser (c.1585G>T)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

DHX32 p.Ala529Ser

c.1585G>T · rs78840782 · VCV2421540

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.3	GERP 0.31, phastCons 0.7
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.068 · regional, not allelic
Overall
CADD	13.81	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 0.00935% African / African-American · 7/74,870 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000558% 9/1,611,766 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,696
Remaining individualsnot grpmax-eligible	0.0016%	62,356
European (non-Finnish)	8.49e-05%	1,178,148

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: DHX32
Protein: p.Ala529Ser
Coding: c.1585G>T
MANE Select: NM_078468 · reported on NM_018180
dbSNP: rs78840782
Type: single nucleotide variant
Location: chr10:125840955 (GRCh38)

Full DHX32 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/dhx32-p-ala529ser (accessed [today's date]).

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