Is DCP2 p.Pro74Leu (c.221C>T) pathogenic?

DCP2 p.Pro74Leu (c.221C>T) is classified Uncertain significance in DCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely pathogenic (0.831); Very rare (popmax 0.00446%, eas).

How common is DCP2 p.Pro74Leu (c.221C>T) in the general population?

DCP2 p.Pro74Leu (c.221C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DCP2 p.Pro74Leu (c.221C>T)?

AlphaMissense predicts likely pathogenic (score 0.831) — an in-silico prediction, not a clinical call.

DCP2 p.Pro74Leu

c.221C>T · rs139105675 · VCV2396568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.831 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.831	likely pathogenic
REVEL	0.519	indeterminate
SaProt	LLR -12.49	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.33	acceptor loss, 8 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.92 · regional, not allelic
Overall
CADD	28.0	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

Grpmax group 0.00446% East Asian · 2/44,838 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00149% 24/1,613,480 alleles · very rare exomes 21/1,461,420 · genomes 3/152,060 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,419
South Asian	0.0022%	45,485
Admixed American	0.00167%	59,890
European (non-Finnish)	0.00161%	62,100

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.Pro74Leu
Coding: c.221C>T
MANE Select: NM_152624
dbSNP: rs139105675
Type: single nucleotide variant
Location: chr5:112992136 (GRCh38)
Gene constraint: LOEUF 0.793 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.25 · 33 PDB

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-pro74leu (accessed [today's date]).

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