Is DPF2 p.Ser390Tyr (c.1169C>A) pathogenic?

DPF2 p.Ser390Tyr (c.1169C>A) is classified Conflicting classifications of pathogenicity in DPF2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-01). AlphaMissense: likely benign (0.1493); Ultra-rare (popmax 0.0194%, mid); Associated with Coffin-Siris syndrome 7.

What condition is associated with DPF2 p.Ser390Tyr (c.1169C>A)?

DPF2 p.Ser390Tyr (c.1169C>A) is associated with Coffin-Siris syndrome 7 (ClinVar).

How common is DPF2 p.Ser390Tyr (c.1169C>A) in the general population?

DPF2 p.Ser390Tyr (c.1169C>A) is ultra-rare (popmax 0.0194%, mid) (gnomAD).

What do computational predictors say about DPF2 p.Ser390Tyr (c.1169C>A)?

AlphaMissense predicts likely benign (score 0.1493) — an in-silico prediction, not a clinical call.

DPF2 p.Ser390Tyr

c.1169C>A · rs765632713 · VCV1678611

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1493 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Coffin-Siris syndrome 7

Computational evidence

Protein change
AlphaMissense	0.1493	likely benign
REVEL	0.352	indeterminate
SaProt	LLR -9.75	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 2.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 5,714 bp · p 1.2e-18 · regional, not allelic
Overall
CADD	22.8	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 0.0194% Middle Eastern · 1/5,152 alleles

Filtering AF 0.00199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.00223% 36/1,612,988 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0194%	5,152
European (non-Finnish)	0.0028%	35,759
Remaining individualsnot grpmax-eligible	0.0016%	62,368
African / African-American	0.00133%	74,912

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.Ser390Tyr
Coding: c.1169C>A
MANE Select: NM_006268
dbSNP: rs765632713
Type: single nucleotide variant
Location: chr11:65351752 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.62 · 9 PDB

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

Disease context

Coffin-Siris syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPF2 p.Arg350His Pathogenic/Likely pathogenic ★★ same condition
DPF2 p.Asp346Asn Likely pathogenic ★★ same condition
DPF2 p.Ala133Pro Uncertain significance ★★ ⚠ same condition
DPF2 c.302-11C>T Likely benign ★★ same condition
DPF2 c.904+1G>T Pathogenic ★ same condition
DPF2 p.Arg300Leu Likely pathogenic ★ same condition
DPF2 p.Asp346Gly Pathogenic ★ same condition
DPF2 p.Cys276Phe Pathogenic ★ 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-ser390tyr (accessed [today's date]).

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