Is DRC1 p.Ser330= (c.990C>T) pathogenic?

DRC1 p.Ser330= (c.990C>T) is classified Likely benign in DRC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.0441%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DRC1 p.Ser330= (c.990C>T)?

DRC1 p.Ser330= (c.990C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DRC1 p.Ser330= (c.990C>T) in the general population?

DRC1 p.Ser330= (c.990C>T) is ultra-rare (popmax 0.0441%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DRC1 p.Ser330=

c.990C>T · rs149344139 · VCV414297

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0441%, nfe)

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 0.73	GERP -2, phastCons 1
Overall
CADD	8.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0441% European (non-Finnish) · 520/1,179,312 alleles

Filtering AF 0.041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0397%

Overall 0.0349% 562/1,612,610 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0441%	2,268
Remaining individualsnot grpmax-eligible	0.0272%	3,671
Finnishnot grpmax-eligible	0.0141%	7,102
Admixed American	0.0133%	7,491
African / African-American	0.0107%	9,350

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.Ser330=
Coding: c.990C>T
MANE Select: NM_145038
dbSNP: rs149344139
Type: single nucleotide variant
Location: chr2:26440479 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 330: 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.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
DRC1 p.Ala473Val 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-ser330 (accessed [today's date]).

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