Is DPF2 p.Arg78Cys (c.232C>T) pathogenic?

DPF2 p.Arg78Cys (c.232C>T) is classified Uncertain significance in DPF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). AlphaMissense: likely pathogenic (0.6337); Very rare (popmax 8.47e-05%, nfe).

How common is DPF2 p.Arg78Cys (c.232C>T) in the general population?

DPF2 p.Arg78Cys (c.232C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DPF2 p.Arg78Cys (c.232C>T)?

AlphaMissense predicts likely pathogenic (score 0.6337) — an in-silico prediction, not a clinical call.

DPF2 p.Arg78Cys

c.232C>T · VCV4807925

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6337 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6337	likely pathogenic
REVEL	0.531	indeterminate
SaProt	LLR -2.86	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
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	25.3	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 8.47e-05% European (non-Finnish) · 1/1,180,012 alleles

Overall 6.84e-05% 1/1,461,826 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: DPF2
Protein: p.Arg78Cys
Coding: c.232C>T
MANE Select: NM_006268
Type: single nucleotide variant
Location: chr11:65341004 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.62 · 9 PDB

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

Similar variants

DPF2 p.Arg78= 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-arg78cys (accessed [today's date]).

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