Is DPF3 p.Asp187Asn (c.559G>A) pathogenic?

DPF3 p.Asp187Asn (c.559G>A) is classified Uncertain significance in DPF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: ambiguous (0.3973); Ultra-rare (popmax 0.0164%, mid).

How common is DPF3 p.Asp187Asn (c.559G>A) in the general population?

DPF3 p.Asp187Asn (c.559G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DPF3 p.Asp187Asn (c.559G>A)?

AlphaMissense predicts ambiguous (score 0.3973) — an in-silico prediction, not a clinical call.

DPF3 p.Asp187Asn

c.559G>A · VCV3504858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3973 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3973	ambiguous
REVEL	0.287	benign-leaning
SaProt	LLR -5.61	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 220 kb · p 0.076 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00273% 44/1,613,708 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
South Asian	0.00549%	18,216
European (non-Finnish)	0.00305%	32,772
East Asian	0.00223%	44,884
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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.Asp187Asn
Coding: c.559G>A
MANE Select: NM_001280542
Type: single nucleotide variant
Location: chr14:72714468 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 73.58 · 8 PDB
Residue 187: the 'disordered' region

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

Similar variants

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
DPF3 c.871+3020G>C 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-asp187asn (accessed [today's date]).

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