Is OFD1 p.Ser731= (c.2193C>T) pathogenic?

OFD1 p.Ser731= (c.2193C>T) is classified Likely benign in OFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-05). Very rare (popmax 0.00591%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with OFD1 p.Ser731= (c.2193C>T)?

OFD1 p.Ser731= (c.2193C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is OFD1 p.Ser731= (c.2193C>T) in the general population?

OFD1 p.Ser731= (c.2193C>T) is very rare (popmax 0.00591%, eas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

OFD1 p.Ser731=

c.2193C>T · VCV3302189

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00591%, eas)

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 -4.7	GERP -4.3
Overall
CADD	2.942	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00591% East Asian · 2/33,830 alleles

Filtering AF 0.000979% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000165% 2/1,211,284 alleles · very rare exomes 2/1,097,701 · genomes 0/113,583 · joint denominator

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: OFD1
Protein: p.Ser731=
Coding: c.2193C>T
MANE Select: NM_003611
Type: single nucleotide variant
Location: chrX:13760653 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 731: the 'mediates the interaction with sdccag8' region; the 'disordered' region

Full OFD1 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

OFD1 p.Ser731Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
OFD1 p.Arg909Ter Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Ala213Gly Uncertain significance ★★ ⚠ same condition
OFD1 p.Ala506Gly Uncertain significance ★★ ⚠ same condition
OFD1 p.Ala856Val Uncertain significance ★★ ⚠ same condition
OFD1 p.Arg263Trp Uncertain significance ★★ ⚠ same condition
OFD1 p.Arg467Ser Uncertain significance ★★ ⚠ same condition
OFD1 p.Arg487Trp 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/ofd1-p-ser731 (accessed [today's date]).

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