Is DCC p.Gly470Asp (c.1409G>A) pathogenic?

DCC p.Gly470Asp (c.1409G>A) is classified Conflicting classifications of pathogenicity in DCC (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.2453); Rare (popmax 0.525%, nfe).

What condition is associated with DCC p.Gly470Asp (c.1409G>A)?

DCC p.Gly470Asp (c.1409G>A) is associated with amenorrhea (ClinVar).

How common is DCC p.Gly470Asp (c.1409G>A) in the general population?

DCC p.Gly470Asp (c.1409G>A) is rare (popmax 0.525%, nfe) (gnomAD).

What do computational predictors say about DCC p.Gly470Asp (c.1409G>A)?

AlphaMissense predicts likely benign (score 0.2453) — an in-silico prediction, not a clinical call.

DCC p.Gly470Asp

c.1409G>A · rs141813053 · VCV187790

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2453 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.525%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Computational evidence

Protein change
AlphaMissense	0.2453	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	25.1	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 0.525% European (non-Finnish) · 6,189/1,179,974 alleles

Filtering AF 0.514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.509%

Overall 0.42% 6,785/1,614,060 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.525%	191
Remaining individualsnot grpmax-eligible	0.402%	249
Middle Eastern	0.313%	319
Finnishnot grpmax-eligible	0.231%	432
Admixed American	0.127%	790
African / African-American	0.0853%	1,173
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,480
South Asian	0.0187%	5,358
East Asian	0.00223%	44,876

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.Gly470Asp
Coding: c.1409G>A
MANE Select: NM_005215
dbSNP: rs141813053
Type: single nucleotide variant
Location: chr18:53157503 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 470: a UniProt-annotated variant site (in mrmv1; likely pathogenic); a β-strand; the fibronectin type-iii 1 domain

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

Disease context

— disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amenorrhea

Similar variants

DCC p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same condition
DCC p.Arg275Ter Pathogenic ★★ same condition
DCC p.Arg879Ter Pathogenic/Likely pathogenic ★★ same condition
DCC p.Gly803Arg Uncertain significance ★★ ⚠ same condition
DCC c.2053+13A>G Benign ★★ same condition
DCC c.2053+9T>C Benign/Likely benign ★★ same condition
DCC c.3130+10A>G Benign ★★ same condition
DCC c.91+7G>A Benign ★★ 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-gly470asp (accessed [today's date]).

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