Is OFD1 p.Ser723= (c.2169G>A) pathogenic?

OFD1 p.Ser723= (c.2169G>A) is classified Likely benign in OFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-20). Very rare (popmax 0.00704%, sas); Associated with Joubert syndrome.

What condition is associated with OFD1 p.Ser723= (c.2169G>A)?

OFD1 p.Ser723= (c.2169G>A) is associated with Joubert syndrome, orofaciodigital syndrome I (ClinVar).

How common is OFD1 p.Ser723= (c.2169G>A) in the general population?

OFD1 p.Ser723= (c.2169G>A) is very rare (popmax 0.00704%, sas) (gnomAD).

OFD1 p.Ser723=

c.2169G>A · rs984001995 · VCV1101667

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00704%, sas)

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 -9.4	GERP -11
Overall
CADD	0.007	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00704% South Asian · 4/56,807 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00141%

Overall 0.000909% 11/1,209,762 alleles · very rare exomes 9/1,097,880 · genomes 2/111,882 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00704%	14,202
Admixed American	0.00436%	22,917
African / African-American	0.0035%	28,561
European (non-Finnish)	0.000335%	298,328

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.Ser723=
Coding: c.2169G>A
MANE Select: NM_003611
dbSNP: rs984001995
Type: single nucleotide variant
Location: chrX:13760629 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 723: 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.Ser723Leu 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-ser723 (accessed [today's date]).

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