Is DCDC2 p.Ser266Arg (c.796A>C) pathogenic?

DCDC2 p.Ser266Arg (c.796A>C) is classified Uncertain significance in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: ambiguous (0.4098); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DCDC2 p.Ser266Arg (c.796A>C)?

DCDC2 p.Ser266Arg (c.796A>C) is associated with Inborn genetic diseases (ClinVar).

How common is DCDC2 p.Ser266Arg (c.796A>C) in the general population?

DCDC2 p.Ser266Arg (c.796A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCDC2 p.Ser266Arg (c.796A>C)?

AlphaMissense predicts ambiguous (score 0.4098) — an in-silico prediction, not a clinical call.

DCDC2 p.Ser266Arg

c.796A>C · VCV4616977

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4098 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4098	ambiguous
REVEL	0.138	moderately benign-leaning
SaProt	LLR -7.68	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

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: DCDC2
Protein: p.Ser266Arg
Coding: c.796A>C
MANE Select: NM_016356
Type: single nucleotide variant
Location: chr6:24278175 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 266: a UniProt-annotated variant site (in nsc); the 'disordered' region

Full DCDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCDC2 p.Ala153Gly Uncertain significance ★★ ⚠ same condition
DCDC2 p.Ala356Pro Uncertain significance ★★ ⚠ same condition
DCDC2 p.Arg130His Uncertain significance ★★ ⚠ same condition
DCDC2 p.Arg379Lys Uncertain significance ★★ ⚠ same condition
DCDC2 p.Asn268Ser Uncertain significance ★★ ⚠ same condition
DCDC2 p.Glu326Asp Uncertain significance ★★ ⚠ same condition
DCDC2 p.Gly406Glu Uncertain significance ★★ ⚠ same condition
DCDC2 p.Gly407Val Uncertain significance ★★ ⚠ same condition

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/dcdc2-p-ser266arg (accessed [today's date]).

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