Is DHPS p.Arg7= (c.21G>A) pathogenic?

DHPS p.Arg7= (c.21G>A) is classified Likely benign in DHPS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-10). Ultra-rare (popmax 0.01%, amr); Associated with DHPS-related disorder.

What condition is associated with DHPS p.Arg7= (c.21G>A)?

DHPS p.Arg7= (c.21G>A) is associated with DHPS-related disorder (ClinVar).

How common is DHPS p.Arg7= (c.21G>A) in the general population?

DHPS p.Arg7= (c.21G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

DHPS p.Arg7=

c.21G>A · VCV3354413

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Conditions

DHPS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -0.83
Overall
CADD	8.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,990 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000435% 7/1,610,952 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,998
European (non-Finnish)	8.48e-05%	1,179,906

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: DHPS
Protein: p.Arg7=
Coding: c.21G>A
MANE Select: NM_001930
Type: single nucleotide variant
Location: chr19:12681746 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.95 · 89 PDB

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

Disease context

DHPS-related disorder

Similar variants

DHPS p.Asn173Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
DHPS c.207+462G>A Benign same condition
DHPS p.Ala68= Benign same condition
DHPS p.Pro145= Likely benign same condition
DHPS p.Ser204= Benign same condition
DHPS p.Ser219= Benign same condition
DHPS p.Glu71Lys Uncertain significance ★★ ⚠ same type
DHPS p.Gly162Arg 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/dhps-p-arg7 (accessed [today's date]).

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