Is DPF3 p.Arg277Trp (c.829C>T) pathogenic?

DPF3 p.Arg277Trp (c.829C>T) is classified Uncertain significance in DPF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). AlphaMissense: likely benign (0.1815); Very rare (popmax 0.0067%, nfe).

How common is DPF3 p.Arg277Trp (c.829C>T) in the general population?

DPF3 p.Arg277Trp (c.829C>T) is very rare (popmax 0.0067%, nfe) (gnomAD).

What do computational predictors say about DPF3 p.Arg277Trp (c.829C>T)?

AlphaMissense predicts likely benign (score 0.1815) — an in-silico prediction, not a clinical call.

DPF3 p.Arg277Trp

c.829C>T · rs771502693 · VCV3085458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1815 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1815	likely benign
REVEL	0.466	indeterminate
SaProt	LLR -12.09	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 0.29, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 220 kb · p 0.076 · regional, not allelic
Overall
CADD	25.2	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 0.0067% European (non-Finnish) · 79/1,179,224 alleles

Filtering AF 0.00547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00506%

Overall 0.00533% 86/1,612,054 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0067%	14,927
African / African-American	0.00535%	18,688
Remaining individualsnot grpmax-eligible	0.0032%	31,214
South Asian	0.0011%	90,590

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.Arg277Trp
Coding: c.829C>T
MANE Select: NM_001280542
dbSNP: rs771502693
Type: single nucleotide variant
Location: chr14:72674282 (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-arg277trp (accessed [today's date]).

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