Is OFD1 p.Pro687= (c.2061G>A) pathogenic?

OFD1 p.Pro687= (c.2061G>A) is classified Likely benign in OFD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-18). Ultra-rare (popmax 0.0241%, mid); Associated with Joubert syndrome.

What condition is associated with OFD1 p.Pro687= (c.2061G>A)?

OFD1 p.Pro687= (c.2061G>A) is associated with Joubert syndrome, orofaciodigital syndrome I, primary ciliary dyskinesia (ClinVar).

How common is OFD1 p.Pro687= (c.2061G>A) in the general population?

OFD1 p.Pro687= (c.2061G>A) is ultra-rare (popmax 0.0241%, mid) (gnomAD).

OFD1 p.Pro687=

c.2061G>A · rs757923355 · VCV588479

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, 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 -4	GERP -8.6
Overall
CADD	0.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0241% Middle Eastern · 1/4,143 alleles

Filtering AF 0.00352% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00213%

Overall 0.000855% 10/1,169,186 alleles · ultra-rare exomes 9/1,057,400 · genomes 1/111,786 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0241%	4,143
Admixed American	0.0104%	9,632
East Asian	0.00597%	16,749
South Asian	0.004%	25,031
European (non-Finnish)	0.000114%	877,208

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.Pro687=
Coding: c.2061G>A
MANE Select: NM_003611
dbSNP: rs757923355
Type: single nucleotide variant
Location: chrX:13760521 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 687: 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 p.Pro687Leu 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-pro687 (accessed [today's date]).

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