Is DCDC2 p.Pro14= (c.42C>T) pathogenic?

DCDC2 p.Pro14= (c.42C>T) is classified Likely benign in DCDC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-04-30). AlphaMissense: likely benign (0.1655); Very rare (popmax 0.005%, amr); Associated with DCDC2-related disorder.

What condition is associated with DCDC2 p.Pro14= (c.42C>T)?

DCDC2 p.Pro14= (c.42C>T) is associated with DCDC2-related disorder (ClinVar).

How common is DCDC2 p.Pro14= (c.42C>T) in the general population?

DCDC2 p.Pro14= (c.42C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about DCDC2 p.Pro14= (c.42C>T)?

AlphaMissense predicts likely benign (score 0.1655) — an in-silico prediction, not a clinical call.

DCDC2 p.Pro14=

c.42C>T · rs1270753724 · VCV3054651

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1655 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DCDC2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1655	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -6.68	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 -1.5	GERP -3.4
Overall
CADD	13.41	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

Grpmax group 0.005% Admixed American · 3/59,988 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00062% 10/1,612,694 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,996
African / African-American	0.004%	24,978
European (non-Finnish)	0.000339%	294,893

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.Pro14=
Coding: c.42C>T
MANE Select: NM_016356
dbSNP: rs1270753724
Type: single nucleotide variant
Location: chr6:24357709 (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

DCDC2-related disorder

Similar variants

DCDC2 c.705-2A>G Pathogenic ★★ same condition
DCDC2 c.557+1G>T Pathogenic ★ same condition
DCDC2 p.Gln448Lys Uncertain significance ★ ⚠ same condition
DCDC2 p.Gln417Ter Likely pathogenic same condition
DCDC2 p.Gly368Glu Uncertain significance ⚠ same condition
DCDC2 p.Lys249Gln Uncertain significance ⚠ same condition
DCDC2 c.1326+6T>G Likely benign same condition
DCDC2 c.704+6T>C Likely benign 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-pro14 (accessed [today's date]).

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