Is OFD1 p.Lys237fs (c.710del) pathogenic?

OFD1 p.Lys237fs (c.710del) is classified Pathogenic in OFD1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-12-21). Ultra-rare (popmax 0.0324%, amr); Associated with Joubert syndrome.

What condition is associated with OFD1 p.Lys237fs (c.710del)?

OFD1 p.Lys237fs (c.710del) is associated with Joubert syndrome, orofaciodigital syndrome I, COACH syndrome (ClinVar).

How common is OFD1 p.Lys237fs (c.710del) in the general population?

OFD1 p.Lys237fs (c.710del) is ultra-rare (popmax 0.0324%, amr) (gnomAD).

OFD1 p.Lys237fs

c.710del · rs312262845 · VCV41142

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0324%, amr)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.2	GERP 1.3, phastCons 1
Overall
CADD	19.32	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0324% Admixed American · 14/43,239 alleles

Filtering AF 0.0195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0156%

Overall 0.00667% 71/1,065,099 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0324%	3,088
African / African-American	0.0165%	6,067
South Asian	0.00567%	17,650
European (non-Finnish)	0.00494%	20,252
Ashkenazi Jewishnot grpmax-eligible	0.00469%	21,305
Remaining individualsnot grpmax-eligible	0.00217%	46,125

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.Lys237fs
Coding: c.710del
MANE Select: NM_003611
dbSNP: rs312262845
Type: Deletion
Location: chrX:13746827 (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 COACH syndrome

Similar variants

OFD1 p.Lys237Arg Uncertain significance ★ ⚠ same residue
OFD1 p.Arg373fs Pathogenic ★★ same condition
OFD1 p.Glu134fs Pathogenic ★★ same condition
OFD1 p.Lys455fs Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Thr551fs Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Tyr916fs Pathogenic ★★ same condition
OFD1 p.Ser323fs Uncertain significance ★★ same condition
OFD1 c.1056-21_1056-18del Likely benign ★★ 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-lys237fs (accessed [today's date]).

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