Is DHX32 p.Ser24Phe (c.71C>T) pathogenic?

DHX32 p.Ser24Phe (c.71C>T) is classified Uncertain significance in DHX32 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-09). AlphaMissense: likely benign (0.1243); Very rare (popmax 0.000169%, nfe).

How common is DHX32 p.Ser24Phe (c.71C>T) in the general population?

DHX32 p.Ser24Phe (c.71C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about DHX32 p.Ser24Phe (c.71C>T)?

AlphaMissense predicts likely benign (score 0.1243) — an in-silico prediction, not a clinical call.

DHX32 p.Ser24Phe

c.71C>T · rs2134073731 · VCV1488502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1243 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1243	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -6.99	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 28 kb · p 0.00028 · regional, not allelic
Overall
CADD	24.4	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 0.000169% European (non-Finnish) · 2/1,180,038 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,874 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: DHX32
Protein: p.Ser24Phe
Coding: c.71C>T
MANE Select: NM_018180
dbSNP: rs2134073731
Type: single nucleotide variant
Location: chr10:125880754 (GRCh38)
Gene constraint: LOEUF 0.919 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.34
Residue 24: the 'disordered' region

Full DHX32 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHX32 p.Ala251Val Uncertain significance ★★ ⚠ same type
DHX32 p.Ala93Thr Uncertain significance ★★ ⚠ same type
DHX32 p.Arg129Gln Uncertain significance ★★ ⚠ same type
DHX32 p.Arg261Cys Uncertain significance ★★ ⚠ same type
DHX32 p.Arg261His Uncertain significance ★★ ⚠ same type
DHX32 p.Asn239Lys Uncertain significance ★★ ⚠ same type
DHX32 p.Asn297His Uncertain significance ★★ ⚠ same type
DHX32 p.Asn297Ile 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/dhx32-p-ser24phe (accessed [today's date]).

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