Is OFD1 p.Val997= (c.2991C>T) pathogenic?

OFD1 p.Val997= (c.2991C>T) is classified Likely benign in OFD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-09). Very rare (popmax 0.00656%, amr); Associated with Joubert syndrome.

What condition is associated with OFD1 p.Val997= (c.2991C>T)?

OFD1 p.Val997= (c.2991C>T) is associated with Joubert syndrome, orofaciodigital syndrome I (ClinVar).

How common is OFD1 p.Val997= (c.2991C>T) in the general population?

OFD1 p.Val997= (c.2991C>T) is very rare (popmax 0.00656%, amr) (gnomAD).

OFD1 p.Val997=

c.2991C>T · rs373088434 · VCV1585083

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00656%, amr)

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>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -11	GERP -9.4
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00656% Admixed American · 3/45,756 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000882%

Overall 0.000668% 8/1,197,826 alleles · very rare exomes 4/1,086,343 · genomes 4/111,483 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00656%	15,252
Remaining individualsnot grpmax-eligible	0.00212%	47,155
African / African-American	0.00176%	56,779
European (non-Finnish)	0.000339%	294,804

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.Val997=
Coding: c.2991C>T
MANE Select: NM_003611
dbSNP: rs373088434
Type: single nucleotide variant
Location: chrX:13768780 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 997: 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.Val997Ala 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
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-val997 (accessed [today's date]).

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