Is DPF2 p.Asp349His (c.1045G>C) pathogenic?

DPF2 p.Asp349His (c.1045G>C) is classified Uncertain significance in DPF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-25). AlphaMissense: likely pathogenic (1); Absent from gnomAD v4.1; Associated with Coffin-Siris syndrome 7.

What condition is associated with DPF2 p.Asp349His (c.1045G>C)?

DPF2 p.Asp349His (c.1045G>C) is associated with Coffin-Siris syndrome 7 (ClinVar).

How common is DPF2 p.Asp349His (c.1045G>C) in the general population?

DPF2 p.Asp349His (c.1045G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPF2 p.Asp349His (c.1045G>C)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

DPF2 p.Asp349His

c.1045G>C · rs373186765 · VCV1321295

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Coffin-Siris syndrome 7

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic · top 9% in DPF2
REVEL	0.838	moderately pathogenic-leaning
SaProt	LLR -17.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 5,714 bp · p 1.2e-18 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPF2
Protein: p.Asp349His
Coding: c.1045G>C
MANE Select: NM_006268
dbSNP: rs373186765
Type: single nucleotide variant
Location: chr11:65348877 (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.Asp349Tyr Uncertain significance ★ ⚠ same residue
DPF2 p.Asp349Asn Pathogenic/Likely pathogenic ★★ same residue
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

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-asp349his (accessed [today's date]).

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