Is DCC p.Arg773His (c.2318G>A) pathogenic?

DCC p.Arg773His (c.2318G>A) is classified Likely benign in DCC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.1466); Ultra-rare (popmax 0.0892%, eas); Associated with DCC-related disorder.

What condition is associated with DCC p.Arg773His (c.2318G>A)?

DCC p.Arg773His (c.2318G>A) is associated with DCC-related disorder (ClinVar).

How common is DCC p.Arg773His (c.2318G>A) in the general population?

DCC p.Arg773His (c.2318G>A) is ultra-rare (popmax 0.0892%, eas) (gnomAD).

What do computational predictors say about DCC p.Arg773His (c.2318G>A)?

AlphaMissense predicts likely benign (score 0.1466) — an in-silico prediction, not a clinical call.

DCC p.Arg773His

c.2318G>A · rs138144679 · VCV3036265

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1466 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0892%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

DCC-related disorder

Computational evidence

Protein change
AlphaMissense	0.1466	likely benign
REVEL	0.255	benign-leaning
SaProt	—	withheld · numbering disagrees past residue 178 · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP -0.83, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0892% East Asian · 40/44,854 alleles

Filtering AF 0.0673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.00353% 57/1,613,872 alleles · ultra-rare exomes 40/1,461,618 · genomes 17/152,254 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0892%	1,121
African / African-American	0.00533%	18,757
Remaining individualsnot grpmax-eligible	0.0032%	31,245
Finnishnot grpmax-eligible	0.00156%	64,028
South Asian	0.0011%	91,078
European (non-Finnish)	0.000763%	131,096

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.Arg773His
Coding: c.2318G>A
MANE Select: NM_005215
dbSNP: rs138144679
Type: single nucleotide variant
Location: chr18:53339866 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 773: a β-strand; the fibronectin type-iii 4 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

DCC-related disorder

Similar variants

DCC c.2828-1G>A Likely pathogenic ★ same condition
DCC c.3898+2T>C Likely pathogenic ★ same condition
DCC p.Arg501Ter Likely pathogenic ★ same condition
DCC p.Glu512Ter Likely pathogenic ★ same condition
DCC p.Trp508Ter Likely pathogenic ★ same condition
DCC p.Trp745Ter Likely pathogenic ★ same condition
DCC p.Arg773Ser Uncertain significance ★ same residue
DCC p.Pro1086Leu 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-arg773his (accessed [today's date]).

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