Is DCDC1 p.Asn159Ser (c.476A>G) pathogenic?

DCDC1 p.Asn159Ser (c.476A>G) is classified Uncertain significance in DCDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-09). AlphaMissense: likely benign (0.0999); Very rare (popmax 0.00168%, amr).

How common is DCDC1 p.Asn159Ser (c.476A>G) in the general population?

DCDC1 p.Asn159Ser (c.476A>G) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about DCDC1 p.Asn159Ser (c.476A>G)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

DCDC1 p.Asn159Ser

c.476A>G · rs2539791898 · VCV2732816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -5.33	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 1.8	GERP 0.74, phastCons 0.7
Regional constraint	o/e 1.13	unconstrained · MANE · 450 kb · p 2.3e-08 · regional, not allelic
Overall
CADD	9.855	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 0.00168% Admixed American · 1/59,374 alleles

Overall 0.000137% 2/1,456,986 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,374
African / African-American	0.00134%	74,754

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.Asn159Ser
Coding: c.476A>G
MANE Select: NM_001387274
dbSNP: rs2539791898
Type: single nucleotide variant
Location: chr11:31306347 (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

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-asn159ser (accessed [today's date]).

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