Is DCDC2 p.Asp167Tyr (c.499G>T) pathogenic?

DCDC2 p.Asp167Tyr (c.499G>T) is classified Uncertain significance in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: ambiguous (0.4247); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DCDC2 p.Asp167Tyr (c.499G>T)?

DCDC2 p.Asp167Tyr (c.499G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCDC2 p.Asp167Tyr (c.499G>T) in the general population?

DCDC2 p.Asp167Tyr (c.499G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCDC2 p.Asp167Tyr (c.499G>T)?

AlphaMissense predicts ambiguous (score 0.4247) — an in-silico prediction, not a clinical call.

DCDC2 p.Asp167Tyr

c.499G>T · rs2532401676 · VCV3080428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4247 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4247	ambiguous
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -13.91	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	27.0	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.Asp167Tyr
Coding: c.499G>T
MANE Select: NM_016356
dbSNP: rs2532401676
Type: single nucleotide variant
Location: chr6:24301773 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 167: the doublecortin 2 domain; an α-helix

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-asp167tyr (accessed [today's date]).

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