Is DCP2 p.Leu339Phe (c.1015C>T) pathogenic?

DCP2 p.Leu339Phe (c.1015C>T) is classified Uncertain significance in DCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.0595); Ultra-rare (popmax 0.0133%, amr).

How common is DCP2 p.Leu339Phe (c.1015C>T) in the general population?

DCP2 p.Leu339Phe (c.1015C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about DCP2 p.Leu339Phe (c.1015C>T)?

AlphaMissense predicts likely benign (score 0.0595) — an in-silico prediction, not a clinical call.

DCP2 p.Leu339Phe

c.1015C>T · VCV4238177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0595 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0595	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	donor loss · deltas
Constraint at this position
Conservation	phyloP 0.057
Regional constraint	o/e 1.13	unconstrained · MANE · 21 kb · p 0.015 · regional, not allelic
Overall
CADD	5.868	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.0133% Admixed American · 8/59,970 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000558% 9/1,613,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,496
European (non-Finnish)	8.48e-05%	1,179,870

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: DCP2
Protein: p.Leu339Phe
Coding: c.1015C>T
MANE Select: NM_152624
Type: single nucleotide variant
Location: chr5:113008010 (GRCh38)
Gene constraint: LOEUF 0.793 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.25 · 33 PDB
Residue 339: the 'disordered' region

Full DCP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCP2 p.Ala390Glu Uncertain significance ★ ⚠ same type
DCP2 p.Arg166Gln Uncertain significance ★ ⚠ same type
DCP2 p.Arg173Cys Uncertain significance ★ ⚠ same type
DCP2 p.Arg241Gln Uncertain significance ★ ⚠ same type
DCP2 p.Arg274Cys Uncertain significance ★ ⚠ same type
DCP2 p.Arg274His Uncertain significance ★ ⚠ same type
DCP2 p.Asn168Asp Uncertain significance ★ ⚠ same type
DCP2 p.Asn187Asp 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/dcp2-p-leu339phe (accessed [today's date]).

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