Is DPF1 p.Glu131Asp (c.393G>T) pathogenic?

DPF1 p.Glu131Asp (c.393G>T) is classified Uncertain significance in DPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely benign (0.067); Ultra-rare (popmax 0.0125%, nfe).

How common is DPF1 p.Glu131Asp (c.393G>T) in the general population?

DPF1 p.Glu131Asp (c.393G>T) is ultra-rare (popmax 0.0125%, nfe) (gnomAD).

What do computational predictors say about DPF1 p.Glu131Asp (c.393G>T)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

DPF1 p.Glu131Asp

c.393G>T · rs370726056 · VCV2352698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0125%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.123	moderately 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 0.57	GERP 1.4, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 12 kb · p 9.7e-16 · regional, not allelic
Overall
CADD	16.85	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 E158D vs ClinVar E131D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0125% European (non-Finnish) · 148/1,180,038 alleles

Filtering AF 0.0109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.01% 162/1,614,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,811
European (non-Finnish)grpmax	0.0125%	7,973
Admixed American	0.00667%	15,002
African / African-American	0.00133%	74,950
South Asian	0.0011%	91,094

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.Glu131Asp
Coding: c.393G>T
MANE Select: NM_001135155
dbSNP: rs370726056
Type: single nucleotide variant
Location: chr19:38218964 (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.Arg230His 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-glu131asp (accessed [today's date]).

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