Is DPF2 p.Asp175Val (c.524A>T) pathogenic?

DPF2 p.Asp175Val (c.524A>T) is classified Uncertain significance in DPF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.657); Very rare (popmax 0.00351%, amr).

How common is DPF2 p.Asp175Val (c.524A>T) in the general population?

DPF2 p.Asp175Val (c.524A>T) is very rare (popmax 0.00351%, amr) (gnomAD).

What do computational predictors say about DPF2 p.Asp175Val (c.524A>T)?

AlphaMissense predicts likely pathogenic (score 0.657) — an in-silico prediction, not a clinical call.

DPF2 p.Asp175Val

c.524A>T · VCV4528155

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.657 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00351%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.657	likely pathogenic
REVEL	0.655	pathogenic-leaning
SaProt	LLR -8.58	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.92 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 10 kb · p 0.0043 · regional, not allelic
Overall
CADD	27.4	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 0.00351% Admixed American · 2/56,940 alleles

Filtering AF 0.000583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000139% 2/1,441,344 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.Asp175Val
Coding: c.524A>T
MANE Select: NM_006268
Type: single nucleotide variant
Location: chr11:65343803 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.62 · 9 PDB
Residue 175: the 'disordered' region

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

Similar variants

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
DPF2 p.Arg83Trp 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-asp175val (accessed [today's date]).

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