Is DCC p.Ile416Ser (c.1247T>G) pathogenic?

DCC p.Ile416Ser (c.1247T>G) is classified Uncertain significance in DCC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-08). AlphaMissense: likely pathogenic (0.6438); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DCC p.Ile416Ser (c.1247T>G)?

DCC p.Ile416Ser (c.1247T>G) is associated with Inborn genetic diseases (ClinVar).

How common is DCC p.Ile416Ser (c.1247T>G) in the general population?

DCC p.Ile416Ser (c.1247T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCC p.Ile416Ser (c.1247T>G)?

AlphaMissense predicts likely pathogenic (score 0.6438) — an in-silico prediction, not a clinical call.

DCC p.Ile416Ser

c.1247T>G · rs2511644851 · VCV2300440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6438 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6438	likely pathogenic
REVEL	0.379	indeterminate
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCC
Protein: p.Ile416Ser
Coding: c.1247T>G
MANE Select: NM_005215
dbSNP: rs2511644851
Type: single nucleotide variant
Location: chr18:53066152 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 416: 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

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-ile416ser (accessed [today's date]).

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