Is DCC p.Asp434Gly (c.1301A>G) pathogenic?

DCC p.Asp434Gly (c.1301A>G) is classified Uncertain significance in DCC (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.5744); Absent from gnomAD v4.1.

How common is DCC p.Asp434Gly (c.1301A>G) in the general population?

DCC p.Asp434Gly (c.1301A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCC p.Asp434Gly (c.1301A>G)?

AlphaMissense predicts likely pathogenic (score 0.5744) — an in-silico prediction, not a clinical call.

DCC p.Asp434Gly

c.1301A>G · rs2144397254 · VCV1049482

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5744	likely pathogenic
REVEL	0.48	indeterminate
SaProt	LLR -9.01	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 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	26.3	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.Asp434Gly
Coding: c.1301A>G
MANE Select: NM_005215
dbSNP: rs2144397254
Type: single nucleotide variant
Location: chr18:53157395 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 434: a UniProt-annotated variant site (in mrmv1; likely pathogenic); the fibronectin type-iii 1 domain

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

Similar variants

DCC p.Arg1021Ter Pathogenic ★★ same type
DCC p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same type
DCC p.Arg275Ter Pathogenic ★★ same type
DCC p.Arg879Ter Pathogenic/Likely pathogenic ★★ same type
DCC c.3620-2A>G Uncertain significance ★★ same type
DCC p.Arg597Gln Uncertain significance ★★ ⚠ same type
DCC p.Gly1294Arg Uncertain significance ★★ ⚠ same type
DCC p.Gly55Arg Uncertain significance ★★ ⚠ 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-asp434gly (accessed [today's date]).

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