Is DCDC2 p.Ala30Val (c.89C>T) pathogenic?

DCDC2 p.Ala30Val (c.89C>T) is classified Uncertain significance in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-27). AlphaMissense: likely benign (0.1642); Very rare (popmax 0.00333%, amr).

How common is DCDC2 p.Ala30Val (c.89C>T) in the general population?

DCDC2 p.Ala30Val (c.89C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DCDC2 p.Ala30Val (c.89C>T)?

AlphaMissense predicts likely benign (score 0.1642) — an in-silico prediction, not a clinical call.

DCDC2 p.Ala30Val

c.89C>T · VCV3361674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1642	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -6.79	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 9.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	23.3	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R8H vs ClinVar A30V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,012 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,613,304 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,006
Remaining individualsnot grpmax-eligible	0.0016%	62,482
South Asian	0.0011%	91,084
European (non-Finnish)	0.000254%	393,345

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: DCDC2
Protein: p.Ala30Val
Coding: c.89C>T
MANE Select: NM_016356
Type: single nucleotide variant
Location: chr6:24357662 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 30: the doublecortin 1 domain

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

Similar variants

DCDC2 p.Ala30Thr Uncertain significance ★ ⚠ same residue
DCDC2 c.294-2A>G Pathogenic ★★ same type
DCDC2 c.349-2A>G Pathogenic ★★ same type
DCDC2 c.705-2A>G Pathogenic ★★ same type
DCDC2 p.Leu297Ter Pathogenic ★★ same type
DCDC2 p.Met1Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
DCDC2 p.Ser128Ter Pathogenic/Likely pathogenic ★★ same type
DCDC2 p.Ala153Gly 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/dcdc2-p-ala30val (accessed [today's date]).

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