Is OFD1 p.Ser684= (c.2052C>T) pathogenic?

OFD1 p.Ser684= (c.2052C>T) is classified Benign in OFD1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.4%, afr); Associated with Joubert syndrome.

What condition is associated with OFD1 p.Ser684= (c.2052C>T)?

OFD1 p.Ser684= (c.2052C>T) is associated with Joubert syndrome, orofaciodigital syndrome I, primary ciliary dyskinesia (ClinVar).

How common is OFD1 p.Ser684= (c.2052C>T) in the general population?

OFD1 p.Ser684= (c.2052C>T) is low-frequency (popmax 3.4%, afr) (gnomAD).

OFD1 p.Ser684=

c.2052C>T · rs61742891 · VCV159468

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.4%, afr)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.7	GERP -6
Overall
CADD	0.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.4% African / African-American · 1,881/55,254 alleles

Filtering AF 3.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.22%

Overall 0.184% 2,154/1,167,500 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.4%	29
Admixed American	0.305%	328
Middle Eastern	0.268%	373
Remaining individualsnot grpmax-eligible	0.261%	383
Ashkenazi Jewishnot grpmax-eligible	0.0105%	9,540
European (non-Finnish)	0.00262%	38,108
South Asian	0.00202%	49,584

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.Ser684=
Coding: c.2052C>T
MANE Select: NM_003611
dbSNP: rs61742891
Type: single nucleotide variant
Location: chrX:13760512 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 684: the 'mediates the interaction with sdccag8' region

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 primary ciliary dyskinesia

Similar variants

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
OFD1 c.2388-3T>C 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-ser684 (accessed [today's date]).

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