Is DPF1 p.Cys286Tyr (c.857G>A) pathogenic?

DPF1 p.Cys286Tyr (c.857G>A) is classified Uncertain significance in DPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). AlphaMissense: ambiguous (0.4318); Very rare (popmax 0.0011%, sas).

How common is DPF1 p.Cys286Tyr (c.857G>A) in the general population?

DPF1 p.Cys286Tyr (c.857G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DPF1 p.Cys286Tyr (c.857G>A)?

AlphaMissense predicts ambiguous (score 0.4318) — an in-silico prediction, not a clinical call.

DPF1 p.Cys286Tyr

c.857G>A · rs2513434054 · VCV2214483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4318 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.4318	ambiguous
REVEL	0.491	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP -0.61, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 12 kb · p 9.7e-16 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM C269Y vs ClinVar C286Y) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 6.84e-05% 1/1,461,786 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: DPF1
Protein: p.Cys286Tyr
Coding: c.857G>A
MANE Select: NM_001135155
dbSNP: rs2513434054
Type: single nucleotide variant
Location: chr19:38216181 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.41

Full DPF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPF1 c.778+2T>G Uncertain significance ★ same type
DPF1 c.-17A>C Uncertain significance ★ same type
DPF1 c.-35C>A Uncertain significance ★ same type
DPF1 p.Ala186Pro Uncertain significance ★ ⚠ same type
DPF1 p.Ala32Thr Uncertain significance ★ same type
DPF1 p.Ala380Ser Uncertain significance ★ same type
DPF1 p.Ala66Asp Uncertain significance ★ same type
DPF1 p.Arg230His 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/dpf1-p-cys286tyr (accessed [today's date]).

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