Is DCX p.Arg178His (c.533G>A) pathogenic?

DCX p.Arg178His (c.533G>A) is classified Likely pathogenic in DCX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). AlphaMissense: likely pathogenic (0.8136); Very rare (popmax 0.00351%, afr).

How common is DCX p.Arg178His (c.533G>A) in the general population?

DCX p.Arg178His (c.533G>A) is very rare (popmax 0.00351%, afr) (gnomAD).

What do computational predictors say about DCX p.Arg178His (c.533G>A)?

AlphaMissense predicts likely pathogenic (score 0.8136) — an in-silico prediction, not a clinical call.

DCX p.Arg178His

c.533G>A · VCV3899812

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8136 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00351%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8136	likely pathogenic ✓ concordant with ClinVar
REVEL	0.75	pathogenic-leaning
SaProt	LLR -13.69	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 77 kb · p 4.4e-24 · regional, not allelic
Overall
CADD	25.8	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 0.00351% African / African-American · 2/56,922 alleles

Filtering AF 0.000583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000248% 3/1,209,345 alleles · very rare exomes 1/1,098,104 · genomes 2/111,241 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00351%	28,461
Remaining individualsnot grpmax-eligible	0.0021%	47,593

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.Arg178His
Coding: c.533G>A
MANE Select: NM_001195553
Type: single nucleotide variant
Location: chrX:111401162 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 178: a UniProt-annotated variant site (in sbhx)

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

Similar variants

DCX p.Arg178Cys Pathogenic/Likely pathogenic ★★ same residue
DCX p.Arg178Gly Pathogenic ★ same residue
DCX p.Arg178= Uncertain significance ★ same residue
DCX p.Arg178Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
DCX c.364+1G>A Likely pathogenic ★★ same type
DCX c.705+1G>A Pathogenic ★★ same type
DCX c.706-2A>G Pathogenic ★★ same type
DCX c.809-1G>A Pathogenic/Likely pathogenic ★★ 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/dcx-p-arg178his (accessed [today's date]).

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