Is DCDC2 p.Lys49Gln (c.145A>C) pathogenic?

DCDC2 p.Lys49Gln (c.145A>C) is classified Uncertain significance in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). AlphaMissense: likely benign (0.2126); Very rare (popmax 0.00133%, afr).

How common is DCDC2 p.Lys49Gln (c.145A>C) in the general population?

DCDC2 p.Lys49Gln (c.145A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DCDC2 p.Lys49Gln (c.145A>C)?

AlphaMissense predicts likely benign (score 0.2126) — an in-silico prediction, not a clinical call.

DCDC2 p.Lys49Gln

c.145A>C · VCV3375847

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2126 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2126	likely benign
REVEL	0.428	indeterminate
SaProt	LLR -9.93	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP -1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 0.00133% African / African-American · 1/74,936 alleles

Overall 0.000657% 1/152,190 alleles · very rare

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.Lys49Gln
Coding: c.145A>C
MANE Select: NM_016356
Type: single nucleotide variant
Location: chr6:24357606 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 49: the doublecortin 1 domain

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

Similar variants

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
DCDC2 p.Ala356Pro 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-lys49gln (accessed [today's date]).

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