Is DRC1 p.Ile225= (c.675T>C) pathogenic?

DRC1 p.Ile225= (c.675T>C) is classified Likely benign in DRC1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-11). Rare (popmax 0.16%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with DRC1 p.Ile225= (c.675T>C)?

DRC1 p.Ile225= (c.675T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DRC1 p.Ile225= (c.675T>C) in the general population?

DRC1 p.Ile225= (c.675T>C) is rare (popmax 0.16%, sas) (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.Ile225=

c.675T>C · rs149032953 · VCV414291

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.16%, sas)

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 -7	GERP -3.4
Overall
CADD	0.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.16% South Asian · 146/91,022 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.022% 355/1,613,846 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.16%	623
Middle Eastern	0.0496%	2,017
European (non-Finnish)	0.0163%	6,145
Remaining individualsnot grpmax-eligible	0.0112%	8,928
Admixed American	0.00833%	11,998
East Asian	0.00223%	44,880
African / African-American	0.00133%	75,020

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.Ile225=
Coding: c.675T>C
MANE Select: NM_145038
dbSNP: rs149032953
Type: single nucleotide variant
Location: chr2:26429762 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 225: 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.Ile225Asn Uncertain significance ★ ⚠ same residue
DRC1 p.Ile225fs Pathogenic ★ same residue
DRC1 p.Ile225Thr 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

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-ile225 (accessed [today's date]).

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