Is DCC p.Glu118= (c.354G>A) pathogenic?

DCC p.Glu118= (c.354G>A) is classified Benign in DCC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-28). Common (popmax 21.8%, mid) — too common for a highly-penetrant pathogenic allele; Associated with gaze palsy, familial horizontal, with progressive scoliosis, 2.

What condition is associated with DCC p.Glu118= (c.354G>A)?

DCC p.Glu118= (c.354G>A) is associated with gaze palsy, familial horizontal, with progressive scoliosis, 2 (ClinVar).

DCC p.Glu118=

Q: How common is DCC p.Glu118= (c.354G>A) in the general population?

DCC p.Glu118= (c.354G>A) is common (popmax 21.8%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Horizontal gaze palsy with progressive scoliosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.354G>A · rs13381333 · VCV1255455

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 21.8%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

gaze palsy, familial horizontal, with progressive scoliosis, 2

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 0.36	GERP -4.3, phastCons 0.93
Overall
CADD	6.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.8% Middle Eastern · 1,320/6,060 alleles

Filtering AF 20.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.4%

Overall 12.5% 201,669/1,613,824 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	21.8%	5
Ashkenazi Jewishnot grpmax-eligible	21.5%	5
European (non-Finnish)	13.8%	7
Remaining individualsnot grpmax-eligible	12.9%	8
Amishnot grpmax-eligible	12.1%	8
South Asian	10.7%	9
Admixed American	8.08%	12
Finnishnot grpmax-eligible	7.76%	13
African / African-American	3.96%	25
East Asian	0.0557%	1,795

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: DCC
Protein: p.Glu118=
Coding: c.354G>A
MANE Select: NM_005215
dbSNP: rs13381333
Type: single nucleotide variant
Location: chr18:52752316 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 118: the ig-like c2-type 1 domain

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

Disease context

gaze palsy, familial horizontal, with progressive scoliosis, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked:

For Horizontal gaze palsy with progressive scoliosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

DCC p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same condition
DCC p.Arg275Ter Pathogenic ★★ same condition
DCC p.Arg879Ter Pathogenic/Likely pathogenic ★★ same condition
DCC p.Gly803Arg Uncertain significance ★★ ⚠ same condition
DCC c.2053+13A>G Benign ★★ same condition
DCC c.2053+9T>C Benign/Likely benign ★★ same condition
DCC c.3130+10A>G Benign ★★ same condition
DCC c.91+7G>A 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/dcc-p-glu118 (accessed [today's date]).

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