Is DCDC1 p.Ala178= (c.534T>G) pathogenic?

DCDC1 p.Ala178= (c.534T>G) is classified Benign in DCDC1 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-25). Common (popmax 7.04%, afr) — too common for a highly-penetrant pathogenic allele.

DCDC1 p.Ala178=

Q: How common is DCDC1 p.Ala178= (c.534T>G) in the general population?

DCDC1 p.Ala178= (c.534T>G) is common (popmax 7.04%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.534T>G · rs16922066 · VCV1951466

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.04%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 2.3, phastCons 1
Overall
CADD	10.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.04% African / African-American · 5,263/74,770 alleles

Filtering AF 6.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.82%

Overall 0.372% 5,997/1,610,386 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.04%	14
Admixed American	0.555%	180
Remaining individualsnot grpmax-eligible	0.481%	208
Middle Eastern	0.198%	504
South Asian	0.0133%	7,539
European (non-Finnish)	0.00671%	14,913

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.Ala178=
Coding: c.534T>G
MANE Select: NM_001387274
dbSNP: rs16922066
Type: single nucleotide variant
Location: chr11:31306289 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.53
Residue 178: the doublecortin 1 domain

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

Similar variants

DCDC1 p.Ala178Val Uncertain significance ★ ⚠ same residue
DCDC1 p.Gln95His Uncertain significance ★★ ⚠ same type
DCDC1 p.Thr239Met Uncertain significance ★★ ⚠ same type
DCDC1 p.Thr317Ala Uncertain significance ★★ ⚠ same type
DCDC1 c.591+13C>T Benign ★★ same type
DCDC1 p.Ala1431Thr Benign ★★ ⚠ same type
DCDC1 p.Glu200= Benign ★★ same type
DCDC1 p.Leu224= Benign ★★ 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/dcdc1-p-ala178 (accessed [today's date]).

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