Is DPF1 p.Arg230His (c.689G>A) pathogenic?

DPF1 p.Arg230His (c.689G>A) is classified Uncertain significance in DPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). Very rare (popmax 8.74e-05%, nfe).

How common is DPF1 p.Arg230His (c.689G>A) in the general population?

DPF1 p.Arg230His (c.689G>A) is very rare (popmax 8.74e-05%, nfe) (gnomAD).

DPF1 p.Arg230His

c.689G>A · VCV3842204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.74e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.358	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP -3.4, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 12 kb · p 9.7e-16 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.74e-05% European (non-Finnish) · 1/1,144,434 alleles

Overall 0.000143% 2/1,395,360 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00167%	59,784
European (non-Finnish)grpmax	8.74e-05%	1,144,435

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DPF1
Protein: p.Arg230His
Coding: c.689G>A
MANE Select: NM_001135155
Type: single nucleotide variant
Location: chr19:38217498 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.41

Full DPF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPF1 c.778+2T>G Uncertain significance ★ same type
DPF1 c.-17A>C Uncertain significance ★ same type
DPF1 c.-35C>A Uncertain significance ★ same type
DPF1 p.Ala186Pro Uncertain significance ★ ⚠ same type
DPF1 p.Ala32Thr Uncertain significance ★ same type
DPF1 p.Ala380Ser Uncertain significance ★ same type
DPF1 p.Ala66Asp Uncertain significance ★ same type
DPF1 p.Arg237Leu 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/dpf1-p-arg230his (accessed [today's date]).

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