Is DPF3 p.Arg175Trp (c.523C>T) pathogenic?

DPF3 p.Arg175Trp (c.523C>T) is classified Uncertain significance in DPF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: likely pathogenic (0.7373); Very rare (popmax 0.00432%, amr).

How common is DPF3 p.Arg175Trp (c.523C>T) in the general population?

DPF3 p.Arg175Trp (c.523C>T) is very rare (popmax 0.00432%, amr) (gnomAD).

What do computational predictors say about DPF3 p.Arg175Trp (c.523C>T)?

AlphaMissense predicts likely pathogenic (score 0.7373) — an in-silico prediction, not a clinical call.

DPF3 p.Arg175Trp

c.523C>T · rs1313292844 · VCV2517590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7373 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7373	likely pathogenic
REVEL	0.479	indeterminate
SaProt	LLR -11.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 220 kb · p 0.076 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00432% Admixed American · 2/46,250 alleles

Filtering AF 0.000717% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000268%

Overall 0.000704% 11/1,561,700 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00432%	23,125
European (non-Finnish)	0.000774%	129,217

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: DPF3
Protein: p.Arg175Trp
Coding: c.523C>T
MANE Select: NM_001280542
dbSNP: rs1313292844
Type: single nucleotide variant
Location: chr14:72723635 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 73.58 · 8 PDB
Residue 175: the 'disordered' region

Full DPF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPF3 p.Arg175Gln Uncertain significance ★ ⚠ same residue
DPF3 c.871+2959C>T Uncertain significance ★★ same type
DPF3 p.Leu85= Benign ★★ same type
DPF3 c.871+2937G>T Uncertain significance ★ same type
DPF3 c.871+2946G>A Uncertain significance ★ same type
DPF3 c.871+2953G>A Uncertain significance ★ same type
DPF3 c.871+2958A>G Uncertain significance ★ same type
DPF3 c.871+3006C>T 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/dpf3-p-arg175trp (accessed [today's date]).

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