Is OFD1 p.Asp1009= (c.3027C>T) pathogenic?

OFD1 p.Asp1009= (c.3027C>T) is classified Conflicting classifications of pathogenicity in OFD1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-02). Very rare (popmax 0.00437%, amr); Associated with Joubert syndrome.

What condition is associated with OFD1 p.Asp1009= (c.3027C>T)?

OFD1 p.Asp1009= (c.3027C>T) is associated with Joubert syndrome, orofaciodigital syndrome I (ClinVar).

How common is OFD1 p.Asp1009= (c.3027C>T) in the general population?

OFD1 p.Asp1009= (c.3027C>T) is very rare (popmax 0.00437%, amr) (gnomAD).

OFD1 p.Asp1009=

c.3027C>T · rs758646234 · VCV1603248

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00437%, amr)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 0.41	GERP 3, phastCons 1
Overall
CADD	0.243	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00437% Admixed American · 2/45,809 alleles

Filtering AF 0.000923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000722%

Overall 0.00478% 57/1,193,190 alleles · very rare exomes 49/1,080,989 · genomes 8/112,201 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.146%	685
Remaining individualsnot grpmax-eligible	0.0191%	5,223
Admixed Americangrpmax	0.00437%	22,905
European (non-Finnish)	0.00159%	62,839

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp1009=
Coding: c.3027C>T
MANE Select: NM_003611
dbSNP: rs758646234
Type: single nucleotide variant
Location: chrX:13769096 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 1009: 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.Asp1009Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
OFD1 p.Asp1009His Uncertain significance ★ ⚠ 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

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-asp1009 (accessed [today's date]).

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