Is DCX p.Pro298Ser (c.892C>T) pathogenic?

DCX p.Pro298Ser (c.892C>T) is classified Uncertain significance in DCX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-30). AlphaMissense: likely benign (0.1213); Ultra-rare (popmax 0.0299%, sas).

How common is DCX p.Pro298Ser (c.892C>T) in the general population?

DCX p.Pro298Ser (c.892C>T) is ultra-rare (popmax 0.0299%, sas) (gnomAD).

What do computational predictors say about DCX p.Pro298Ser (c.892C>T)?

AlphaMissense predicts likely benign (score 0.1213) — an in-silico prediction, not a clinical call.

DCX p.Pro298Ser

c.892C>T · rs780994284 · VCV423012

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1213 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0299%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1213	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -8.70	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 31 kb · p 0.075 · regional, not allelic
Overall
CADD	23.3	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 0.0299% South Asian · 17/56,861 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0156%

Overall 0.00198% 24/1,210,534 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0299%	3,345
Remaining individualsnot grpmax-eligible	0.0063%	15,869
European (non-Finnish)	0.000447%	223,838

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.Pro298Ser
Coding: c.892C>T
MANE Select: NM_001195553
dbSNP: rs780994284
Type: single nucleotide variant
Location: chrX:111330958 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 298: the 'disordered' region

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

Similar variants

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
DCX p.Ala204Asp Pathogenic ★★ same type
DCX p.Ala251Ser Pathogenic ★★ same type
DCX p.Arg178Cys Pathogenic/Likely pathogenic ★★ same type
DCX p.Arg186Cys 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-pro298ser (accessed [today's date]).

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