Is DCC p.Ala893Thr (c.2677G>A) pathogenic?

DCC p.Ala893Thr (c.2677G>A) is classified Pathogenic in DCC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-01-01). AlphaMissense: likely benign (0.2487); Very rare (popmax 8.72e-05%, nfe); Associated with corpus callosum, agenesis of.

What condition is associated with DCC p.Ala893Thr (c.2677G>A)?

DCC p.Ala893Thr (c.2677G>A) is associated with corpus callosum, agenesis of (ClinVar).

How common is DCC p.Ala893Thr (c.2677G>A) in the general population?

DCC p.Ala893Thr (c.2677G>A) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about DCC p.Ala893Thr (c.2677G>A)?

AlphaMissense predicts likely benign (score 0.2487) — an in-silico prediction, not a clinical call.

DCC p.Ala893Thr

c.2677G>A · rs1057519057 · VCV375287

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2487 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

corpus callosum, agenesis of

Computational evidence

Protein change
AlphaMissense	0.2487	likely benign ⚠ discordant with ClinVar
REVEL	0.074	moderately benign-leaning
SaProt	LLR -3.14	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 8.7	GERP 0.33, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	22.4	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 8.72e-05% European (non-Finnish) · 1/1,146,984 alleles

Overall 7.01e-05% 1/1,425,724 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.Ala893Thr
Coding: c.2677G>A
MANE Select: NM_005215
dbSNP: rs1057519057
Type: single nucleotide variant
Location: chr18:53391876 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 893: the fibronectin type-iii 5 domain; a UniProt-annotated variant site (in mrmv1; likely pathogenic); a UniProt-annotated variant site (in mrmv1; uncertain significance)

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

Disease context

corpus callosum, agenesis of — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCC p.Arg275Ter Pathogenic ★★ same condition
DCC p.Met743Leu Uncertain significance ★ ⚠ same condition
DCC p.Val754Met Uncertain significance ★ ⚠ same condition
DCC p.Arg597Pro Pathogenic same condition
DCC p.Gly805Glu Pathogenic same condition
DCC p.Val793Gly Pathogenic same condition
DCC p.Thr309fs Pathogenic same condition
DCC p.Arg1021Ter Pathogenic ★★ 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-ala893thr (accessed [today's date]).

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