Is DCP1B p.Ile166Phe (c.496A>T) pathogenic?

DCP1B p.Ile166Phe (c.496A>T) is classified Uncertain significance in DCP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1515); Very rare (popmax 0.00669%, eas).

How common is DCP1B p.Ile166Phe (c.496A>T) in the general population?

DCP1B p.Ile166Phe (c.496A>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about DCP1B p.Ile166Phe (c.496A>T)?

AlphaMissense predicts likely benign (score 0.1515) — an in-silico prediction, not a clinical call.

DCP1B p.Ile166Phe

c.496A>T · VCV4658780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1515 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1515	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.84, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 58 kb · p 0.25 · regional, not allelic
Overall
CADD	16.69	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 0.00669% East Asian · 3/44,844 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000205% 3/1,461,394 alleles · very rare

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: DCP1B
Protein: p.Ile166Phe
Coding: c.496A>T
MANE Select: NM_152640
Type: single nucleotide variant
Location: chr12:1965584 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.19

Full DCP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCP1B p.Pro567= Benign ★★ same type
DCP1B p.Ser301Thr Benign ★★ same type
DCP1B p.Ala302Thr Uncertain significance ★ ⚠ same type
DCP1B p.Ala387Val Uncertain significance ★ ⚠ same type
DCP1B p.Ala475Thr Uncertain significance ★ ⚠ same type
DCP1B p.Ala520Val Uncertain significance ★ ⚠ same type
DCP1B p.Ala585Thr Uncertain significance ★ ⚠ same type
DCP1B p.Ala612Thr 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/dcp1b-p-ile166phe (accessed [today's date]).

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