Is DPF1 p.Ala186Pro (c.556G>C) pathogenic?

DPF1 p.Ala186Pro (c.556G>C) is classified Uncertain significance in DPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-20). AlphaMissense: likely benign (0.0954); Ultra-rare (popmax 0.0147%, afr).

How common is DPF1 p.Ala186Pro (c.556G>C) in the general population?

DPF1 p.Ala186Pro (c.556G>C) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about DPF1 p.Ala186Pro (c.556G>C)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

DPF1 p.Ala186Pro

c.556G>C · VCV4014538

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.261	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -0.71, phastCons 0.96
Regional constraint	o/e 0.65	unconstrained · MANE · 12 kb · p 9.7e-16 · regional, not allelic
Overall
CADD	18.91	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A213P vs ClinVar A186P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,910 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000682% 11/1,613,976 alleles · ultra-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: DPF1
Protein: p.Ala186Pro
Coding: c.556G>C
MANE Select: NM_001135155
Type: single nucleotide variant
Location: chr19:38217837 (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.Ala32Thr Uncertain significance ★ same type
DPF1 p.Ala380Ser Uncertain significance ★ same type
DPF1 p.Ala66Asp Uncertain significance ★ same type
DPF1 p.Arg230His 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-ala186pro (accessed [today's date]).

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