Is OFD1 p.Phe193= (c.579C>T) pathogenic?

OFD1 p.Phe193= (c.579C>T) is classified Likely benign in OFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-19). Ultra-rare (popmax 0.0537%, mid); Associated with Joubert syndrome.

What condition is associated with OFD1 p.Phe193= (c.579C>T)?

OFD1 p.Phe193= (c.579C>T) is associated with Joubert syndrome, orofaciodigital syndrome I (ClinVar).

How common is OFD1 p.Phe193= (c.579C>T) in the general population?

OFD1 p.Phe193= (c.579C>T) is ultra-rare (popmax 0.0537%, mid) (gnomAD).

OFD1 p.Phe193=

c.579C>T · rs780256374 · VCV1623230

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0537%, mid)

Conditions

Joubert syndrome

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 2.4	GERP -0.85, phastCons 1
Overall
CADD	1.475	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0537% Middle Eastern · 2/3,723 alleles

Filtering AF 0.00949% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00397%

Overall 0.0015% 18/1,203,885 alleles · ultra-rare exomes 16/1,091,758 · genomes 2/112,127 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0537%	1,862
Remaining individualsnot grpmax-eligible	0.0127%	7,897
Admixed American	0.00219%	45,752
South Asian	0.00177%	56,633
European (non-Finnish)	0.000899%	111,275

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.Phe193=
Coding: c.579C>T
MANE Select: NM_003611
dbSNP: rs780256374
Type: single nucleotide variant
Location: chrX:13746380 (GRCh38)
Structure: AlphaFold pLDDT 68.41

Full OFD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: orofaciodigital syndrome I

Similar variants

OFD1 p.Phe193Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
OFD1 c.1411+1G>A Pathogenic ★★ same condition
OFD1 c.2600-1G>C Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Arg367Ter Pathogenic ★★ same condition
OFD1 p.Arg41Ter Pathogenic ★★ same condition
OFD1 p.Arg890Ter Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Arg909Ter Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Tyr87Cys Pathogenic ★★ ⚠ 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-phe193 (accessed [today's date]).

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