Is DPF2 p.Leu167Phe (c.499C>T) pathogenic?

DPF2 p.Leu167Phe (c.499C>T) is classified Uncertain significance in DPF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-29). AlphaMissense: ambiguous (0.509); Ultra-rare (popmax 0.0209%, mid).

How common is DPF2 p.Leu167Phe (c.499C>T) in the general population?

DPF2 p.Leu167Phe (c.499C>T) is ultra-rare (popmax 0.0209%, mid) (gnomAD).

What do computational predictors say about DPF2 p.Leu167Phe (c.499C>T)?

AlphaMissense predicts ambiguous (score 0.509) — an in-silico prediction, not a clinical call.

DPF2 p.Leu167Phe

c.499C>T · rs1381561532 · VCV2976948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.509 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, mid)

Computational evidence

Protein change
AlphaMissense	0.509	ambiguous
REVEL	0.369	indeterminate
SaProt	LLR -7.02	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 10 kb · p 0.0043 · regional, not allelic
Overall
CADD	23.5	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 0.0209% Middle Eastern · 1/4,776 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000313% 5/1,598,378 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0209%	4,776
European (non-Finnish)	0.000341%	293,198

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.Leu167Phe
Coding: c.499C>T
MANE Select: NM_006268
dbSNP: rs1381561532
Type: single nucleotide variant
Location: chr11:65343778 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.62 · 9 PDB
Residue 167: the 'disordered' region

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

Similar variants

DPF2 p.Leu167= Likely benign same residue
DPF2 c.904+1G>A Pathogenic ★★ same type
DPF2 p.Arg350His Pathogenic/Likely pathogenic ★★ same type
DPF2 p.Asp346Asn Likely pathogenic ★★ same type
DPF2 p.Asp349Asn Pathogenic/Likely pathogenic ★★ same type
DPF2 p.Ala133Pro Uncertain significance ★★ ⚠ same type
DPF2 p.Arg38His Uncertain significance ★★ ⚠ same type
DPF2 p.Arg77Gln 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/dpf2-p-leu167phe (accessed [today's date]).

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