Is DRC2 p.Arg118Cys (c.352C>T) pathogenic?

DRC2 p.Arg118Cys (c.352C>T) is classified Uncertain significance in DRC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-12). AlphaMissense: likely benign (0.0977); Ultra-rare (popmax 0.0922%, sas); Associated with Inborn genetic diseases.

What condition is associated with DRC2 p.Arg118Cys (c.352C>T)?

DRC2 p.Arg118Cys (c.352C>T) is associated with Inborn genetic diseases, primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Arg118Cys (c.352C>T) in the general population?

DRC2 p.Arg118Cys (c.352C>T) is ultra-rare (popmax 0.0922%, sas) (gnomAD).

What do computational predictors say about DRC2 p.Arg118Cys (c.352C>T)?

AlphaMissense predicts likely benign (score 0.0977) — an in-silico prediction, not a clinical call.

DRC2 p.Arg118Cys

c.352C>T · rs377299600 · VCV2196699

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0977 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0922%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0977	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -9.67	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 2.7	GERP 0.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.19 · regional, not allelic
Overall
CADD	23.1	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 0.0922% South Asian · 84/91,082 alleles

Filtering AF 0.0763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0704%

Overall 0.00663% 107/1,613,988 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0922%	1,084
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00267%	37,461
European (non-Finnish)	0.00153%	65,555

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: DRC2
Protein: p.Arg118Cys
Coding: c.352C>T
MANE Select: NM_033124
dbSNP: rs377299600
Type: single nucleotide variant
Location: chr12:48914455 (GRCh38)
Structure: AlphaFold pLDDT 83.21 · 1 PDB

Full DRC2 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

Also linked: primary ciliary dyskinesia 27

Similar variants

CCDC65 p.Arg70Gln Uncertain significance ★★ ⚠ same condition
CCDC65 p.Glu110Lys Uncertain significance ★★ ⚠ same condition
CCDC65 p.Lys158Asn Uncertain significance ★★ ⚠ same condition
DRC2 p.Ala109Val Uncertain significance ★★ ⚠ same condition
DRC2 p.Ala114Pro Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg294His Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg315Gln Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg433Leu 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/drc2-p-arg118cys (accessed [today's date]).

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