Is DCDC1 p.Phe187Ser (c.560T>C) pathogenic?

DCDC1 p.Phe187Ser (c.560T>C) is classified Uncertain significance in DCDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: ambiguous (0.3601); Very rare (popmax 0.00135%, afr).

How common is DCDC1 p.Phe187Ser (c.560T>C) in the general population?

DCDC1 p.Phe187Ser (c.560T>C) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about DCDC1 p.Phe187Ser (c.560T>C)?

AlphaMissense predicts ambiguous (score 0.3601) — an in-silico prediction, not a clinical call.

DCDC1 p.Phe187Ser

c.560T>C · VCV4009701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Computational evidence

Protein change
AlphaMissense	0.3601	ambiguous
REVEL	0.598	indeterminate
SaProt	LLR -5.58	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.21, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 450 kb · p 2.3e-08 · regional, not allelic
Overall
CADD	16.45	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 0.00135% African / African-American · 1/74,244 alleles

Overall 6.25e-05% 1/1,599,308 alleles · very rare exomes 0/1,447,134 · genomes 1/152,174 · joint denominator

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.Phe187Ser
Coding: c.560T>C
MANE Select: NM_001387274
Type: single nucleotide variant
Location: chr11:31306263 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.53
Residue 187: the doublecortin 1 domain

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

Similar variants

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
DCDC1 p.Lys1494Arg 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-phe187ser (accessed [today's date]).

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