Is DCDC2B p.Ala55Ser (c.163G>T) pathogenic?

DCDC2B p.Ala55Ser (c.163G>T) is classified Uncertain significance in DCDC2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely benign (0.0968); Absent from gnomAD v4.1.

How common is DCDC2B p.Ala55Ser (c.163G>T) in the general population?

DCDC2B p.Ala55Ser (c.163G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCDC2B p.Ala55Ser (c.163G>T)?

AlphaMissense predicts likely benign (score 0.0968) — an in-silico prediction, not a clinical call.

DCDC2B p.Ala55Ser

c.163G>T · VCV4237993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0968 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0968	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -5.19	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 2.3	GERP -1.4, phastCons 0.99
Regional constraint	o/e 1.06	unconstrained · MANE · 6,800 bp · p 0.21 · regional, not allelic
Overall
CADD	15.79	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

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: DCDC2B
Protein: p.Ala55Ser
Coding: c.163G>T
MANE Select: NM_001099434
Type: single nucleotide variant
Location: chr1:32209256 (GRCh38)
Gene constraint: LOEUF 1.383 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.12
Residue 55: the doublecortin 1 domain

Full DCDC2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCDC2B p.Ala55Val Uncertain significance ★ ⚠ same residue
DCDC2B p.Ala125Pro Uncertain significance ★ ⚠ same type
DCDC2B p.Ala187Gly Uncertain significance ★ ⚠ same type
DCDC2B p.Ala239Ser Uncertain significance ★ ⚠ same type
DCDC2B p.Ala291Thr Uncertain significance ★ ⚠ same type
DCDC2B p.Ala346Val Uncertain significance ★ ⚠ same type
DCDC2B p.Ala69Glu Uncertain significance ★ ⚠ same type
DCDC2B p.Ala69Thr 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/dcdc2b-p-ala55ser (accessed [today's date]).

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