Is DCC p.Arg201Gly (c.601C>G) pathogenic?

DCC p.Arg201Gly (c.601C>G) is classified Benign in DCC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-28). AlphaMissense: likely benign (0.1946); Common (popmax 62.4%, sas) — too common for a highly-penetrant pathogenic allele.

What condition is associated with DCC p.Arg201Gly (c.601C>G)?

DCC p.Arg201Gly (c.601C>G) is associated with gaze palsy, familial horizontal, with progressive scoliosis, 2 (ClinVar).

What do computational predictors say about DCC p.Arg201Gly (c.601C>G)?

AlphaMissense predicts likely benign (score 0.1946) — an in-silico prediction, not a clinical call.

DCC p.Arg201Gly

Q: How common is DCC p.Arg201Gly (c.601C>G) in the general population?

DCC p.Arg201Gly (c.601C>G) is common (popmax 62.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.601C>G · rs2229080 · VCV803493

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1946 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 62.4%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Computational evidence

Protein change
AlphaMissense	0.1946	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -4.97	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 0.34	GERP -4, phastCons 0.28
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	14.77	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 62.4% South Asian · 56,798/91,066 alleles

Filtering AF 61.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 61.8%

Overall 39.2% 632,232/1,613,528 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	62.4%	2
East Asian	60.1%	2
Admixed American	57.1%	2
Amishnot grpmax-eligible	49.8%	2
Ashkenazi Jewishnot grpmax-eligible	49.3%	2
Middle Eastern	46.9%	2
Remaining individualsnot grpmax-eligible	41.3%	2
Finnishnot grpmax-eligible	39.5%	3
European (non-Finnish)	35.6%	3
African / African-American	33.7%	3

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.Arg201Gly
Coding: c.601C>G
MANE Select: NM_005215
dbSNP: rs2229080
Type: single nucleotide variant
Location: chr18:52906232 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 201: a disulfide bond; a UniProt-annotated variant site (in); the ig-like c2-type 2 domain

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

Disease context

— disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gaze palsy, familial horizontal, with progressive scoliosis, 2

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-arg201gly (accessed [today's date]).

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