Is DCC p.Thr361= (c.1083T>G) pathogenic?

DCC p.Thr361= (c.1083T>G) is classified Likely benign in DCC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Very rare (popmax 8.48e-05%, nfe).

How common is DCC p.Thr361= (c.1083T>G) in the general population?

DCC p.Thr361= (c.1083T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DCC p.Thr361=

c.1083T>G · rs781473932 · VCV793420

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 0.35	GERP -1.4, phastCons 1
Overall
CADD	7.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,642 alleles

Overall 0.000744% 12/1,612,406 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,931
Remaining individualsnot grpmax-eligible	0.00801%	12,486
European (non-Finnish)grpmax	8.48e-05%	1,178,642

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr361=
Coding: c.1083T>G
MANE Select: NM_005215
dbSNP: rs781473932
Type: single nucleotide variant
Location: chr18:53063402 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 361: a disulfide bond; a UniProt-annotated variant site (in mrmv1; likely pathogenic); the ig-like c2-type 4 domain

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

Similar variants

DCC p.Thr361Ala Uncertain significance ★ ⚠ same residue
DCC p.Arg1021Ter Pathogenic ★★ same type
DCC p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same type
DCC p.Arg275Ter Pathogenic ★★ same type
DCC p.Arg879Ter Pathogenic/Likely pathogenic ★★ same type
DCC c.3620-2A>G Uncertain significance ★★ same type
DCC p.Arg597Gln Uncertain significance ★★ ⚠ same type
DCC p.Gly1294Arg 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/dcc-p-thr361 (accessed [today's date]).

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