Is DCC p.Arg211Gln (c.632G>A) pathogenic?

DCC p.Arg211Gln (c.632G>A) is classified Uncertain significance in DCC (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-22). AlphaMissense: likely benign (0.1196); Ultra-rare (popmax 0.0174%, afr).

How common is DCC p.Arg211Gln (c.632G>A) in the general population?

DCC p.Arg211Gln (c.632G>A) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about DCC p.Arg211Gln (c.632G>A)?

AlphaMissense predicts likely benign (score 0.1196) — an in-silico prediction, not a clinical call.

DCC p.Arg211Gln

c.632G>A · VCV4975120

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1196 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Computational evidence

Protein change
AlphaMissense	0.1196	likely benign
REVEL	0.328	indeterminate
SaProt	—	withheld · numbering disagrees past residue 178 · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	25.7	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 0.0174% African / African-American · 13/74,912 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00198% 32/1,613,916 alleles · ultra-rare exomes 25/1,461,760 · genomes 7/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,762
East Asian	0.00223%	44,872
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.00144%	69,414

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.Arg211Gln
Coding: c.632G>A
MANE Select: NM_005215
Type: single nucleotide variant
Location: chr18:52906263 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 211: the ig-like c2-type 2 domain

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

Similar variants

DCC p.Arg211Pro Uncertain significance ★ ⚠ same residue
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

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-arg211gln (accessed [today's date]).

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