Is DPF1 p.Ala380Ser (c.1138G>T) pathogenic?

DPF1 p.Ala380Ser (c.1138G>T) is classified Uncertain significance in DPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely pathogenic (0.8618); Very rare (popmax 8.48e-05%, nfe).

How common is DPF1 p.Ala380Ser (c.1138G>T) in the general population?

DPF1 p.Ala380Ser (c.1138G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DPF1 p.Ala380Ser (c.1138G>T)?

AlphaMissense predicts likely pathogenic (score 0.8618) — an in-silico prediction, not a clinical call.

DPF1 p.Ala380Ser

c.1138G>T · rs775485375 · VCV3085439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8618 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.8618	likely pathogenic
REVEL	0.571	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 12 kb · p 9.7e-16 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A373S vs ClinVar A380S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,750 alleles

Overall 0.000657% 1/152,206 alleles · very 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.Ala380Ser
Coding: c.1138G>T
MANE Select: NM_001135155
dbSNP: rs775485375
Type: single nucleotide variant
Location: chr19:38212089 (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.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-ala380ser (accessed [today's date]).

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