Is DCXR p.Ser38Arg (c.114C>G) pathogenic?

DCXR p.Ser38Arg (c.114C>G) is classified Uncertain significance in DCXR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely pathogenic (0.9808); Ultra-rare (popmax 0.0139%, afr).

How common is DCXR p.Ser38Arg (c.114C>G) in the general population?

DCXR p.Ser38Arg (c.114C>G) is ultra-rare (popmax 0.0139%, afr) (gnomAD).

What do computational predictors say about DCXR p.Ser38Arg (c.114C>G)?

AlphaMissense predicts likely pathogenic (score 0.9808) — an in-silico prediction, not a clinical call.

DCXR p.Ser38Arg

c.114C>G · rs773008120 · VCV2393048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9808 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0139%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9808	likely pathogenic · top 2% in DCXR
REVEL	0.221	benign-leaning
SaProt	LLR -12.62	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -2.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,719 bp · p 0.43 · regional, not allelic
Overall
CADD	21.3	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 0.0139% African / African-American · 10/71,888 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00571%

Overall 0.0013% 20/1,536,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0139%	7,189
South Asian	0.00119%	84,012
European (non-Finnish)	0.000783%	127,638

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: DCXR
Protein: p.Ser38Arg
Coding: c.114C>G
MANE Select: NM_016286
dbSNP: rs773008120
Type: single nucleotide variant
Location: chr17:82037486 (GRCh38)
Gene constraint: LOEUF 1.362 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 3 PDB
Residue 38: a β-strand; a binding site

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

Similar variants

DCXR c.53-8C>T Benign ★★ same type
DCXR c.52+1G>A Uncertain significance ★ same type
DCXR p.Ala110Val Uncertain significance ★ ⚠ same type
DCXR p.Ala155Ser Uncertain significance ★ ⚠ same type
DCXR p.Ala189Thr Uncertain significance ★ ⚠ same type
DCXR p.Ala6Val Uncertain significance ★ ⚠ same type
DCXR p.Ala87Val Uncertain significance ★ ⚠ same type
DCXR p.Ala99Thr Uncertain significance ★ ⚠ 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/dcxr-p-ser38arg (accessed [today's date]).

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