Is DPF2 p.Asp141Gly (c.422A>G) pathogenic?

DPF2 p.Asp141Gly (c.422A>G) is classified Uncertain significance in DPF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-06). AlphaMissense: likely benign (0.1636); Ultra-rare (popmax 0.0176%, sas); Associated with Inborn genetic diseases.

What condition is associated with DPF2 p.Asp141Gly (c.422A>G)?

DPF2 p.Asp141Gly (c.422A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DPF2 p.Asp141Gly (c.422A>G) in the general population?

DPF2 p.Asp141Gly (c.422A>G) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

What do computational predictors say about DPF2 p.Asp141Gly (c.422A>G)?

AlphaMissense predicts likely benign (score 0.1636) — an in-silico prediction, not a clinical call.

DPF2 p.Asp141Gly

c.422A>G · rs761879535 · VCV2880802

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1636 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1636	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -6.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 10 kb · p 0.0043 · regional, not allelic
Overall
CADD	25.6	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 0.0176% South Asian · 16/91,094 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00118% 19/1,614,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,693
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	8.47e-05%	1,180,030

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.Asp141Gly
Coding: c.422A>G
MANE Select: NM_006268
dbSNP: rs761879535
Type: single nucleotide variant
Location: chr11:65341519 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.62 · 9 PDB
Residue 141: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPF2 p.Asp141Asn Uncertain significance ★ ⚠ same residue
DPF2 c.904+1G>A Pathogenic ★★ same condition
DPF2 p.Ala133Pro Uncertain significance ★★ ⚠ same condition
DPF2 p.Arg77Gln Uncertain significance ★★ ⚠ same condition
DPF2 p.Arg83Trp Uncertain significance ★★ ⚠ same condition
DPF2 p.Asn26Ser Uncertain significance ★★ ⚠ same condition
DPF2 p.Glu173Gly Uncertain significance ★★ ⚠ same condition
DPF2 p.Gly189Val Uncertain significance ★★ ⚠ same condition

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-asp141gly (accessed [today's date]).

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