Is DPF2 p.Leu377Val (c.1129C>G) pathogenic?

DPF2 p.Leu377Val (c.1129C>G) is classified Conflicting classifications of pathogenicity in DPF2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-23). AlphaMissense: likely benign (0.1519); Absent from gnomAD v4.1.

How common is DPF2 p.Leu377Val (c.1129C>G) in the general population?

DPF2 p.Leu377Val (c.1129C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPF2 p.Leu377Val (c.1129C>G)?

AlphaMissense predicts likely benign (score 0.1519) — an in-silico prediction, not a clinical call.

DPF2 p.Leu377Val

c.1129C>G · rs1854701811 · VCV2017631

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1519 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1519	likely benign
REVEL	0.513	indeterminate
SaProt	LLR -9.22	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 2.6	GERP 0.12, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 5,714 bp · p 1.2e-18 · regional, not allelic
Overall
CADD	23.2	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

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.Leu377Val
Coding: c.1129C>G
MANE Select: NM_006268
dbSNP: rs1854701811
Type: single nucleotide variant
Location: chr11:65351712 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.62 · 9 PDB
Residue 377: an α-helix

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

Similar variants

DPF2 c.904+1G>A Pathogenic ★★ same type
DPF2 p.Arg350His Pathogenic/Likely pathogenic ★★ same type
DPF2 p.Asp346Asn Likely pathogenic ★★ same type
DPF2 p.Asp349Asn Pathogenic/Likely pathogenic ★★ same type
DPF2 p.Ala133Pro Uncertain significance ★★ ⚠ same type
DPF2 p.Arg38His Uncertain significance ★★ ⚠ same type
DPF2 p.Arg77Gln Uncertain significance ★★ ⚠ same type
DPF2 p.Arg83Trp 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/dpf2-p-leu377val (accessed [today's date]).

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