Is DCDC2 p.Pro119Leu (c.356C>T) pathogenic?

DCDC2 p.Pro119Leu (c.356C>T) is classified Uncertain significance in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely pathogenic (0.7951); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DCDC2 p.Pro119Leu (c.356C>T)?

DCDC2 p.Pro119Leu (c.356C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCDC2 p.Pro119Leu (c.356C>T) in the general population?

DCDC2 p.Pro119Leu (c.356C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCDC2 p.Pro119Leu (c.356C>T)?

AlphaMissense predicts likely pathogenic (score 0.7951) — an in-silico prediction, not a clinical call.

DCDC2 p.Pro119Leu

c.356C>T · rs771269411 · VCV3080427

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7951	likely pathogenic
REVEL	0.439	indeterminate
SaProt	LLR -12.82	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	32.0	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

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.Pro119Leu
Coding: c.356C>T
MANE Select: NM_016356
dbSNP: rs771269411
Type: single nucleotide variant
Location: chr6:24302037 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB

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.Pro119Ser Uncertain significance ★★ ⚠ same residue
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

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-pro119leu (accessed [today's date]).

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