Is DPF3 p.Leu85= (c.253T>C) pathogenic?

DPF3 p.Leu85= (c.253T>C) is classified Benign in DPF3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-27). Common (popmax 29%, sas) — too common for a highly-penetrant pathogenic allele.

DPF3 p.Leu85=

Q: How common is DPF3 p.Leu85= (c.253T>C) in the general population?

DPF3 p.Leu85= (c.253T>C) is common (popmax 29%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.253T>C · rs3742836 · VCV1238152

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 29%, sas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -1.4, phastCons 1
Overall
CADD	9.851	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 29% South Asian · 26,410/90,978 alleles

Filtering AF 28.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.6%

Overall 26.6% 429,328/1,613,002 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	30.4%	3
South Asiangrpmax	29%	3
European (non-Finnish)	28.3%	4
Amishnot grpmax-eligible	27.1%	4
Middle Eastern	27%	4
Remaining individualsnot grpmax-eligible	26.9%	4
East Asian	21.7%	5
Admixed American	21.5%	5
Finnishnot grpmax-eligible	16.5%	6
African / African-American	10.4%	10

Ashkenazi Jewish 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: DPF3
Protein: p.Leu85=
Coding: c.253T>C
MANE Select: NM_001280542
dbSNP: rs3742836
Type: single nucleotide variant
Location: chr14:72753312 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 73.58 · 8 PDB

Full DPF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPF3 c.871+2959C>T Uncertain significance ★★ same type
DPF3 c.871+2937G>T Uncertain significance ★ same type
DPF3 c.871+2946G>A Uncertain significance ★ same type
DPF3 c.871+2953G>A Uncertain significance ★ same type
DPF3 c.871+2958A>G Uncertain significance ★ same type
DPF3 c.871+3006C>T Uncertain significance ★ same type
DPF3 c.871+3020G>C Uncertain significance ★ same type
DPF3 c.871+3078A>G 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/dpf3-p-leu85 (accessed [today's date]).

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