Is DPF2 p.Thr102Ile (c.305C>T) pathogenic?

DPF2 p.Thr102Ile (c.305C>T) is classified Uncertain significance in DPF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-09). AlphaMissense: likely benign (0.0868); Very rare (popmax 8.47e-05%, nfe).

How common is DPF2 p.Thr102Ile (c.305C>T) in the general population?

DPF2 p.Thr102Ile (c.305C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DPF2 p.Thr102Ile (c.305C>T)?

AlphaMissense predicts likely benign (score 0.0868) — an in-silico prediction, not a clinical call.

DPF2 p.Thr102Ile

c.305C>T · VCV3687183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0868 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0868	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.35 · evaluated, not missing
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	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 8.47e-05% European (non-Finnish) · 1/1,180,040 alleles

Overall 0.000657% 1/152,202 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.Thr102Ile
Coding: c.305C>T
MANE Select: NM_006268
Type: single nucleotide variant
Location: chr11:65341402 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.62 · 9 PDB
Residue 102: the 'disordered' region

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

Similar variants

DPF2 p.Thr102= 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-thr102ile (accessed [today's date]).

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