Is DRC4 p.Lys13Arg (c.38A>G) pathogenic?

DRC4 p.Lys13Arg (c.38A>G) is classified Benign in DRC4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-17). AlphaMissense: likely benign (0.0727); Low-frequency (popmax 3.76%, afr); Associated with primary ciliary dyskinesia 33.

What condition is associated with DRC4 p.Lys13Arg (c.38A>G)?

DRC4 p.Lys13Arg (c.38A>G) is associated with primary ciliary dyskinesia 33 (ClinVar).

How common is DRC4 p.Lys13Arg (c.38A>G) in the general population?

DRC4 p.Lys13Arg (c.38A>G) is low-frequency (popmax 3.76%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DRC4 p.Lys13Arg (c.38A>G)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

DRC4 p.Lys13Arg

c.38A>G · rs61734732 · VCV475564

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.76%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 33

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -8.62	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 3.3	GERP 2.1, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 21 kb · p 0.0024 · regional, not allelic
Overall
CADD	16.58	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 3.76% African / African-American · 2,825/75,058 alleles

Filtering AF 3.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.6%

Overall 0.19% 3,068/1,614,190 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.76%	27
Remaining individualsnot grpmax-eligible	0.197%	508
Middle Eastern	0.181%	551
Admixed American	0.137%	732
South Asian	0.00329%	30,363
East Asian	0.00223%	44,880
European (non-Finnish)	0.00195%	51,305

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: DRC4
Protein: p.Lys13Arg
Coding: c.38A>G
MANE Select: NM_001481
dbSNP: rs61734732
Type: single nucleotide variant
Location: chr16:90027670 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 13: the 'regulates microtubule-binding' region; the 'disordered' region

Full DRC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 33 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DRC4 c.495+1G>T Likely pathogenic ★★ same condition
DRC4 p.Gln357Ter Pathogenic ★★ same condition
DRC4 p.Ala280Thr Uncertain significance ★★ ⚠ same condition
DRC4 p.Ala460Pro Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg143Trp Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg164Trp Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg203Gln Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg278Cys 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/drc4-p-lys13arg (accessed [today's date]).

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