Is DCC p.Ile1080Val (c.3238A>G) pathogenic?

DCC p.Ile1080Val (c.3238A>G) is classified Uncertain significance in DCC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-19). AlphaMissense: likely benign (0.1339); Ultra-rare (popmax 0.0134%, afr); Associated with Inborn genetic diseases.

What condition is associated with DCC p.Ile1080Val (c.3238A>G)?

DCC p.Ile1080Val (c.3238A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DCC p.Ile1080Val (c.3238A>G) in the general population?

DCC p.Ile1080Val (c.3238A>G) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

What do computational predictors say about DCC p.Ile1080Val (c.3238A>G)?

AlphaMissense predicts likely benign (score 0.1339) — an in-silico prediction, not a clinical call.

DCC p.Ile1080Val

c.3238A>G · rs906133735 · VCV2366933

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1339 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1339	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -5.44	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 4.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	18.34	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% African / African-American · 10/74,854 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00149% 24/1,613,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,485
Admixed American	0.005%	19,993
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000847%	117,997

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.Ile1080Val
Coding: c.3238A>G
MANE Select: NM_005215
dbSNP: rs906133735
Type: single nucleotide variant
Location: chr18:53450508 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 1080: a UniProt-annotated variant site (in mrmv1; likely pathogenic)

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.Ile1080Phe Uncertain significance ★ ⚠ same residue
DCC p.Arg1021Ter Pathogenic ★★ same condition
DCC p.Arg597Gln Uncertain significance ★★ ⚠ same condition
DCC p.Gly84Arg 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
DCC c.986-3C>T 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-ile1080val (accessed [today's date]).

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