Is DPF2 p.Pro134Leu (c.401C>T) pathogenic?

DPF2 p.Pro134Leu (c.401C>T) is classified Conflicting classifications of pathogenicity in DPF2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-23). AlphaMissense: likely benign (0.0571); Ultra-rare (popmax 0.016%, afr); Associated with Inborn genetic diseases.

What condition is associated with DPF2 p.Pro134Leu (c.401C>T)?

DPF2 p.Pro134Leu (c.401C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DPF2 p.Pro134Leu (c.401C>T) in the general population?

DPF2 p.Pro134Leu (c.401C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about DPF2 p.Pro134Leu (c.401C>T)?

AlphaMissense predicts likely benign (score 0.0571) — an in-silico prediction, not a clinical call.

DPF2 p.Pro134Leu

c.401C>T · rs762767384 · VCV1374936

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0571 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0571	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -5.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 10 kb · p 0.0043 · regional, not allelic
Overall
CADD	23.9	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 0.016% African / African-American · 12/74,916 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00316% 51/1,614,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,243
Admixed American	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.0064%	15,623
East Asian	0.00223%	44,902
South Asian	0.0022%	45,541
European (non-Finnish)	0.00212%	47,202
Finnishnot grpmax-eligible	0.00156%	64,040

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: DPF2
Protein: p.Pro134Leu
Coding: c.401C>T
MANE Select: NM_006268
dbSNP: rs762767384
Type: single nucleotide variant
Location: chr11:65341498 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.62 · 9 PDB
Residue 134: the 'disordered' region

Full DPF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPF2 p.Pro134Ser Uncertain significance ★ ⚠ same residue
DPF2 c.904+1G>A Pathogenic ★★ same condition
DPF2 p.Ala133Pro Uncertain significance ★★ ⚠ same condition
DPF2 p.Arg77Gln Uncertain significance ★★ ⚠ same condition
DPF2 p.Arg83Trp Uncertain significance ★★ ⚠ same condition
DPF2 p.Asn26Ser Uncertain significance ★★ ⚠ same condition
DPF2 p.Asp141Gly Uncertain significance ★★ ⚠ same condition
DPF2 p.Glu173Gly Uncertain significance ★★ ⚠ same condition

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/dpf2-p-pro134leu (accessed [today's date]).

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