Is DCC p.Ile1116Phe (c.3346A>T) pathogenic?

DCC p.Ile1116Phe (c.3346A>T) is classified Uncertain significance in DCC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.3276); Ultra-rare (popmax 0.0148%, afr); Associated with Inborn genetic diseases.

What condition is associated with DCC p.Ile1116Phe (c.3346A>T)?

DCC p.Ile1116Phe (c.3346A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCC p.Ile1116Phe (c.3346A>T) in the general population?

DCC p.Ile1116Phe (c.3346A>T) is ultra-rare (popmax 0.0148%, afr) (gnomAD).

What do computational predictors say about DCC p.Ile1116Phe (c.3346A>T)?

AlphaMissense predicts likely benign (score 0.3276) — an in-silico prediction, not a clinical call.

DCC p.Ile1116Phe

c.3346A>T · VCV4009684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3276 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3276	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -7.61	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 1.8	GERP -3.2, phastCons 0.081
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	13.47	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 0.0148% African / African-American · 11/74,412 alleles

Filtering AF 0.00821% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00637%

Overall 0.000682% 11/1,612,412 alleles · ultra-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.Ile1116Phe
Coding: c.3346A>T
MANE Select: NM_005215
Type: single nucleotide variant
Location: chr18:53450616 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 1116: 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.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
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-ile1116phe (accessed [today's date]).

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