Is DCX p.Ala286Ser (c.856G>T) pathogenic?

DCX p.Ala286Ser (c.856G>T) is classified Benign/Likely benign in DCX (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-24). AlphaMissense: likely benign (0.07); Ultra-rare (popmax 0.0563%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DCX p.Ala286Ser (c.856G>T)?

DCX p.Ala286Ser (c.856G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCX p.Ala286Ser (c.856G>T) in the general population?

DCX p.Ala286Ser (c.856G>T) is ultra-rare (popmax 0.0563%, nfe) (gnomAD).

What do computational predictors say about DCX p.Ala286Ser (c.856G>T)?

AlphaMissense predicts likely benign (score 0.07) — an in-silico prediction, not a clinical call.

DCX p.Ala286Ser

c.856G>T · rs149495971 · VCV210836

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.07 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0563%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.07	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 31 kb · p 0.075 · regional, not allelic
Overall
CADD	20.9	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 0.0563% European (non-Finnish) · 504/895,208 alleles

Filtering AF 0.0522% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0506%

Overall 0.0485% 587/1,210,214 alleles · ultra-rare exomes 550/1,097,965 · genomes 37/112,249 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0735%	1,361
European (non-Finnish)grpmax	0.0563%	1,776
South Asian	0.0475%	2,104
Finnishnot grpmax-eligible	0.0236%	4,239
Middle Eastern	0.023%	4,352
Admixed American	0.0131%	7,637
African / African-American	0.00524%	19,101

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DCX
Protein: p.Ala286Ser
Coding: c.856G>T
MANE Select: NM_001195553
dbSNP: rs149495971
Type: single nucleotide variant
Location: chrX:111330994 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 286: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCX p.Ala286Val Uncertain significance ★ ⚠ same residue
DCX p.Arg196His Pathogenic/Likely pathogenic ★★ same condition
DCX p.Arg39Ter Pathogenic ★★ same condition
DCX p.Ala295Thr Uncertain significance ★★ ⚠ same condition
DCX p.Cys35Arg Uncertain significance ★★ ⚠ same condition
DCX p.Ile107Thr Uncertain significance ★★ ⚠ same condition
DCX c.706-4A>G Benign/Likely benign ★★ same condition
DCX p.Ala316= Benign/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/dcx-p-ala286ser (accessed [today's date]).

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