Is DCXR p.Ser115= (c.345G>A) pathogenic?

DCXR p.Ser115= (c.345G>A) is classified Benign in DCXR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Common (popmax 58%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DCXR-related disorder.

What condition is associated with DCXR p.Ser115= (c.345G>A)?

DCXR p.Ser115= (c.345G>A) is associated with DCXR-related disorder (ClinVar).

DCXR p.Ser115=

Q: How common is DCXR p.Ser115= (c.345G>A) in the general population?

DCXR p.Ser115= (c.345G>A) is common (popmax 58%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.345G>A · rs9780 · VCV3055361

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 58%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

DCXR-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -2.7, phastCons 0.005
Overall
CADD	3.669	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 58% African / African-American · 43,400/74,838 alleles

Filtering AF 57.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 57.3%

Overall 13.4% 215,864/1,613,272 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	58%	2
Finnishnot grpmax-eligible	15.2%	7
Remaining individualsnot grpmax-eligible	12.6%	8
European (non-Finnish)	12.1%	8
Amishnot grpmax-eligible	9.87%	10
Admixed American	8.4%	12
East Asian	6.5%	15
Middle Eastern	5.69%	18
Ashkenazi Jewishnot grpmax-eligible	4.99%	20
South Asian	2.42%	41

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.Ser115=
Coding: c.345G>A
MANE Select: NM_016286
dbSNP: rs9780
Type: single nucleotide variant
Location: chr17:82036724 (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 115: an α-helix

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

Disease context

DCXR-related disorder

Similar variants

DCXR c.150+6T>C Benign same condition
DCXR p.Val212Ile Likely benign ⚠ same condition
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

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-ser115 (accessed [today's date]).

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