Is DCC p.Asn176Asp (c.526A>G) pathogenic?

DCC p.Asn176Asp (c.526A>G) is classified Uncertain significance in DCC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-25). AlphaMissense: likely benign (0.2513); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with DCC p.Asn176Asp (c.526A>G)?

DCC p.Asn176Asp (c.526A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DCC p.Asn176Asp (c.526A>G) in the general population?

DCC p.Asn176Asp (c.526A>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about DCC p.Asn176Asp (c.526A>G)?

AlphaMissense predicts likely benign (score 0.2513) — an in-silico prediction, not a clinical call.

DCC p.Asn176Asp

c.526A>G · rs201156075 · VCV2206998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2513 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2513	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -3.06	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 7	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	21.9	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00186% 30/1,614,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
African / African-American	0.008%	12,508
Remaining individualsnot grpmax-eligible	0.0032%	31,256
Admixed American	0.00167%	60,006
European (non-Finnish)	0.00161%	62,107

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.Asn176Asp
Coding: c.526A>G
MANE Select: NM_005215
dbSNP: rs201156075
Type: single nucleotide variant
Location: chr18:52906157 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 176: a disulfide bond; a UniProt-annotated variant site (in mrmv1; uncertain significance; no effect on interaction with ntn1); the ig-like c2-type 2 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-asn176asp (accessed [today's date]).

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