Is DPF3 p.Cys78Trp (c.234C>G) pathogenic?

DPF3 p.Cys78Trp (c.234C>G) is classified Uncertain significance in DPF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.9728); Very rare (popmax 0.00133%, afr).

How common is DPF3 p.Cys78Trp (c.234C>G) in the general population?

DPF3 p.Cys78Trp (c.234C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DPF3 p.Cys78Trp (c.234C>G)?

AlphaMissense predicts likely pathogenic (score 0.9728) — an in-silico prediction, not a clinical call.

DPF3 p.Cys78Trp

c.234C>G · VCV4661921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9728 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9728	likely pathogenic
REVEL	0.476	indeterminate
SaProt	LLR -13.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 220 kb · p 0.076 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,038 alleles

Overall 6.84e-05% 1/1,461,106 alleles · very rare

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.Cys78Trp
Coding: c.234C>G
MANE Select: NM_001280542
Type: single nucleotide variant
Location: chr14:72753331 (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 p.Leu85= Benign ★★ 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

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-cys78trp (accessed [today's date]).

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