Is OFD1 p.Ser862= (c.2586A>G) pathogenic?

OFD1 p.Ser862= (c.2586A>G) is classified Likely benign in OFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-23). Absent from gnomAD v4.1; Associated with Joubert syndrome.

What condition is associated with OFD1 p.Ser862= (c.2586A>G)?

OFD1 p.Ser862= (c.2586A>G) is associated with Joubert syndrome, orofaciodigital syndrome I (ClinVar).

How common is OFD1 p.Ser862= (c.2586A>G) in the general population?

OFD1 p.Ser862= (c.2586A>G) is absent from gnomAD v4.1 (gnomAD).

OFD1 p.Ser862=

c.2586A>G · rs2518971671 · VCV2035670

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -3.2	GERP -11
Overall
CADD	0.122	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OFD1
Protein: p.Ser862=
Coding: c.2586A>G
MANE Select: NM_003611
dbSNP: rs2518971671
Type: single nucleotide variant
Location: chrX:13763842 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 862: the 'mediates the interaction with sdccag8' region; the 'disordered' 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

Similar variants

OFD1 p.Ser862Ala 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-ser862 (accessed [today's date]).

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