Is DCDC1 p.Phe556fs (c.1668del) pathogenic?

DCDC1 p.Phe556fs (c.1668del) is classified Benign in DCDC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-25). Low-frequency (popmax 1.56%, afr); Associated with DCDC1-related disorder.

What condition is associated with DCDC1 p.Phe556fs (c.1668del)?

DCDC1 p.Phe556fs (c.1668del) is associated with DCDC1-related disorder (ClinVar).

How common is DCDC1 p.Phe556fs (c.1668del) in the general population?

DCDC1 p.Phe556fs (c.1668del) is low-frequency (popmax 1.56%, afr) (gnomAD).

DCDC1 p.Phe556fs

c.1668del · rs556059169 · VCV3042435

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 1.56%, afr)

Conditions

DCDC1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.3	GERP 0.42, phastCons 0.013
Overall
CADD	18.77	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.56% African / African-American · 922/59,186 alleles

Filtering AF 1.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.44%

Overall 0.132% 1,009/766,074 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.56%	64
Remaining individualsnot grpmax-eligible	0.12%	836
Admixed American	0.0611%	1,637
Middle Eastern	0.0225%	4,436
South Asian	0.00402%	24,871
European (non-Finnish)	0.0012%	83,558

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: DCDC1
Protein: p.Phe556fs
Coding: c.1668del
MANE Select: NM_001387274
dbSNP: rs556059169
Type: Deletion
Location: chr11:31106880 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.53

Full DCDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DCDC1-related disorder

Similar variants

DCDC1 c.5234-7_5234-6del Benign same condition
DCDC1 p.Cys1699Ter Likely pathogenic ★ same condition
DCDC1 c.164+3A>G Likely benign same condition
DCDC1 c.1983+10T>C Likely benign same condition
DCDC1 c.2298+8C>T Benign same condition
DCDC1 c.2716-10C>A Benign same condition
DCDC1 c.5233+7A>G Likely benign same condition
DCDC1 c.961-10dup 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/dcdc1-p-phe556fs (accessed [today's date]).

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