Is OFD1 p.Ser337fs (c.1007dup) pathogenic?

OFD1 p.Ser337fs (c.1007dup) is classified Conflicting classifications of pathogenicity in OFD1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-11-17). Ultra-rare (popmax 0.0413%, amr); Associated with Joubert syndrome.

What condition is associated with OFD1 p.Ser337fs (c.1007dup)?

OFD1 p.Ser337fs (c.1007dup) is associated with Joubert syndrome, Simpson-Golabi-Behmel syndrome type 2, orofaciodigital syndrome I (ClinVar).

How common is OFD1 p.Ser337fs (c.1007dup) in the general population?

OFD1 p.Ser337fs (c.1007dup) is ultra-rare (popmax 0.0413%, amr) (gnomAD).

OFD1 p.Ser337fs

c.1007dup · rs749448671 · VCV220124

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, 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 10 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 0.99

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0413% Admixed American · 19/45,967 alleles

Filtering AF 0.027% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0225%

Overall 0.00193% 21/1,090,574 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0413%	2,419
Remaining individualsnot grpmax-eligible	0.00422%	23,702

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.Ser337fs
Coding: c.1007dup
MANE Select: NM_003611
dbSNP: rs749448671
Type: Duplication
Location: chrX:13751317 (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: Simpson-Golabi-Behmel syndrome type 2 orofaciodigital syndrome I primary ciliary dyskinesia

Similar variants

OFD1 p.Leu144fs Pathogenic ★★ same condition
OFD1 p.Leu535fs Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Tyr238fs Pathogenic ★★ same condition
OFD1 c.2757+4dup Uncertain significance ★★ same condition
OFD1 c.1129+15dup Benign/Likely benign ★★ same condition
OFD1 c.829-287dup Benign/Likely benign ★★ same condition
OFD1 p.Ala661fs Pathogenic ★ same condition
OFD1 p.Arg602fs Likely 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-ser337fs (accessed [today's date]).

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