Is DCC p.Asn702Ser (c.2105A>G) pathogenic?

DCC p.Asn702Ser (c.2105A>G) is classified Conflicting classifications of pathogenicity in DCC (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1907); Rare (popmax 0.505%, nfe).

How common is DCC p.Asn702Ser (c.2105A>G) in the general population?

DCC p.Asn702Ser (c.2105A>G) is rare (popmax 0.505%, nfe) (gnomAD).

What do computational predictors say about DCC p.Asn702Ser (c.2105A>G)?

AlphaMissense predicts likely benign (score 0.1907) — an in-silico prediction, not a clinical call.

DCC p.Asn702Ser

c.2105A>G · rs35691189 · VCV187792

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1907 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.505%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Computational evidence

Protein change
AlphaMissense	0.1907	likely benign
REVEL	0.802	moderately pathogenic-leaning
SaProt	LLR -7.63	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
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	23.7	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 0.505% European (non-Finnish) · 5,941/1,176,470 alleles

Filtering AF 0.494% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.49%

Overall 0.402% 6,469/1,610,312 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.505%	198
Remaining individualsnot grpmax-eligible	0.295%	339
Finnishnot grpmax-eligible	0.261%	383
Admixed American	0.108%	923
African / African-American	0.0707%	1,415
Middle Eastern	0.0661%	1,512
South Asian	0.0505%	1,978
Ashkenazi Jewishnot grpmax-eligible	0.0237%	4,225
East Asian	0.00446%	22,417

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.Asn702Ser
Coding: c.2105A>G
MANE Select: NM_005215
dbSNP: rs35691189
Type: single nucleotide variant
Location: chr18:53322098 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 702: the fibronectin type-iii 3 domain; a UniProt-annotated variant site (in mrmv1; likely pathogenic)

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

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-asn702ser (accessed [today's date]).

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