Is DPF2 p.Leu111Pro (c.332T>C) pathogenic?

DPF2 p.Leu111Pro (c.332T>C) is classified Conflicting classifications of pathogenicity in DPF2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-31). AlphaMissense: likely benign (0.1109); Ultra-rare (popmax 0.0223%, eas); Associated with Inborn genetic diseases.

What condition is associated with DPF2 p.Leu111Pro (c.332T>C)?

DPF2 p.Leu111Pro (c.332T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DPF2 p.Leu111Pro (c.332T>C) in the general population?

DPF2 p.Leu111Pro (c.332T>C) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about DPF2 p.Leu111Pro (c.332T>C)?

AlphaMissense predicts likely benign (score 0.1109) — an in-silico prediction, not a clinical call.

DPF2 p.Leu111Pro

c.332T>C · VCV3273575

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1109 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1109	likely benign
REVEL	0.587	indeterminate
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.71, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 10 kb · p 0.0043 · regional, not allelic
Overall
CADD	23.7	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 0.0223% East Asian · 10/44,902 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.000681% 11/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,490
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Leu111Pro
Coding: c.332T>C
MANE Select: NM_006268
Type: single nucleotide variant
Location: chr11:65341429 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.62 · 9 PDB
Residue 111: 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 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
DPF2 p.Gly189Val 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-leu111pro (accessed [today's date]).

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