Is OFD1 p.Val539= (c.1617T>G) pathogenic?

OFD1 p.Val539= (c.1617T>G) is classified Likely benign in OFD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-01). Absent from gnomAD v4.1; Associated with orofaciodigital syndrome I.

What condition is associated with OFD1 p.Val539= (c.1617T>G)?

OFD1 p.Val539= (c.1617T>G) is associated with orofaciodigital syndrome I, Joubert syndrome (ClinVar).

How common is OFD1 p.Val539= (c.1617T>G) in the general population?

OFD1 p.Val539= (c.1617T>G) is absent from gnomAD v4.1 (gnomAD).

OFD1 p.Val539=

c.1617T>G · rs1156292139 · VCV749707

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

orofaciodigital syndrome I

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 · T>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.38	GERP 2.1
Overall
CADD	0.588	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.Val539=
Coding: c.1617T>G
MANE Select: NM_003611
dbSNP: rs1156292139
Type: single nucleotide variant
Location: chrX:13758411 (GRCh38)
Structure: AlphaFold pLDDT 68.41

Full OFD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

orofaciodigital syndrome I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome

Similar variants

OFD1 p.Val539Ala 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-val539 (accessed [today's date]).

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