Is DRC1 p.Ser453= (c.1359C>T) pathogenic?

DRC1 p.Ser453= (c.1359C>T) is classified Benign/Likely benign in DRC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 6.65%, sas) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DRC1 p.Ser453= (c.1359C>T)?

DRC1 p.Ser453= (c.1359C>T) is associated with primary ciliary dyskinesia (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

DRC1 p.Ser453=

Q: How common is DRC1 p.Ser453= (c.1359C>T) in the general population?

DRC1 p.Ser453= (c.1359C>T) is common (popmax 6.65%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1359C>T · rs77226260 · VCV414287

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 6.65%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.2
Overall
CADD	0.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.65% South Asian · 6,059/91,066 alleles

Filtering AF 6.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.46%

Overall 0.738% 11,907/1,614,062 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	6.65%	15
East Asian	5.02%	20
African / African-American	3.38%	30
Remaining individualsnot grpmax-eligible	1.14%	88
Admixed American	0.313%	319
Middle Eastern	0.247%	404
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,742
European (non-Finnish)	0.0106%	9,440
Finnishnot grpmax-eligible	0.00312%	32,002

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: DRC1
Protein: p.Ser453=
Coding: c.1359C>T
MANE Select: NM_145038
dbSNP: rs77226260
Type: single nucleotide variant
Location: chr2:26444911 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 453: a UniProt-annotated variant site (in cild21; multiple flagellar abnormalities are present in patient sperm); a UniProt-annotated variant site (in spgf80); a UniProt-annotated variant site (in cild21)

Full DRC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia — 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

DRC1 p.Ser453Cys Uncertain significance ★★ ⚠ same residue
DRC1 p.Gln118Ter Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Gln337Ter Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Ser642Ter Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Ala250Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala391Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala416Gly Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala45Val 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/drc1-p-ser453 (accessed [today's date]).

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