Is DCC p.Ile183Val (c.547A>G) pathogenic?

DCC p.Ile183Val (c.547A>G) is classified Likely benign in DCC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.1141); Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DCC p.Ile183Val (c.547A>G)?

DCC p.Ile183Val (c.547A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DCC p.Ile183Val (c.547A>G) in the general population?

DCC p.Ile183Val (c.547A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DCC p.Ile183Val (c.547A>G)?

AlphaMissense predicts likely benign (score 0.1141) — an in-silico prediction, not a clinical call.

DCC p.Ile183Val

c.547A>G · VCV4009686

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1141 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1141	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -5.46	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 -1.3	GERP -4
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	0.095	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 0.000254% European (non-Finnish) · 3/1,180,022 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,954 alleles · very rare

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.Ile183Val
Coding: c.547A>G
MANE Select: NM_005215
Type: single nucleotide variant
Location: chr18:52906178 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 183: a disulfide bond; the ig-like c2-type 2 domain

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

Disease context

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

Similar variants

DCC p.Ile183= Likely benign ★ same residue
DCC p.Arg1021Ter Pathogenic ★★ same condition
DCC p.Arg597Gln Uncertain significance ★★ ⚠ same condition
DCC p.Gly84Arg Uncertain significance ★★ ⚠ same condition
DCC p.Ile1080Val Uncertain significance ★★ ⚠ same condition
DCC p.Gln486Leu Benign ★★ ⚠ same condition
DCC p.Arg215Ter Pathogenic ★ same condition
DCC c.3392+4G>A Uncertain significance ★ 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-ile183val (accessed [today's date]).

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