Is DCP1B p.Pro393Ser (c.1177C>T) pathogenic?

DCP1B p.Pro393Ser (c.1177C>T) is classified Uncertain significance in DCP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.0642); Ultra-rare (popmax 0.0267%, eas).

How common is DCP1B p.Pro393Ser (c.1177C>T) in the general population?

DCP1B p.Pro393Ser (c.1177C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about DCP1B p.Pro393Ser (c.1177C>T)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

DCP1B p.Pro393Ser

c.1177C>T · rs181969069 · VCV2390251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -6.30	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 0.34	GERP -0.83, phastCons 0.002
Regional constraint	o/e 0.96	unconstrained · MANE · 58 kb · p 0.25 · regional, not allelic
Overall
CADD	7.711	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 0.0267% East Asian · 12/44,870 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00204% 33/1,614,172 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,739
Admixed American	0.0133%	7,502
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000763%	131,115

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.Pro393Ser
Coding: c.1177C>T
MANE Select: NM_152640
dbSNP: rs181969069
Type: single nucleotide variant
Location: chr12:1952763 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.19
Residue 393: the 'disordered' region

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-pro393ser (accessed [today's date]).

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