Is DPF2 p.Leu122Val (c.364C>G) pathogenic?

DPF2 p.Leu122Val (c.364C>G) is classified Uncertain significance in DPF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-30). AlphaMissense: ambiguous (0.553); Absent from gnomAD v4.1; Associated with Coffin-Siris syndrome 7.

What condition is associated with DPF2 p.Leu122Val (c.364C>G)?

DPF2 p.Leu122Val (c.364C>G) is associated with Coffin-Siris syndrome 7 (ClinVar).

How common is DPF2 p.Leu122Val (c.364C>G) in the general population?

DPF2 p.Leu122Val (c.364C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPF2 p.Leu122Val (c.364C>G)?

AlphaMissense predicts ambiguous (score 0.553) — an in-silico prediction, not a clinical call.

DPF2 p.Leu122Val

c.364C>G · rs1854369385 · VCV930733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.553 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Coffin-Siris syndrome 7

Computational evidence

Protein change
AlphaMissense	0.553	ambiguous
REVEL	0.494	indeterminate
SaProt	LLR -7.29	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 10 kb · p 0.0043 · regional, not allelic
Overall
CADD	20.6	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

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.Leu122Val
Coding: c.364C>G
MANE Select: NM_006268
dbSNP: rs1854369385
Type: single nucleotide variant
Location: chr11:65341461 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.62 · 9 PDB
Residue 122: the 'disordered' region

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-leu122val (accessed [today's date]).

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