Is OFD1 p.Val307Ala (c.920T>C) pathogenic?

OFD1 p.Val307Ala (c.920T>C) is classified Uncertain significance in OFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). AlphaMissense: likely benign (0.1674); Absent from gnomAD v4.1; Associated with Joubert syndrome.

What condition is associated with OFD1 p.Val307Ala (c.920T>C)?

OFD1 p.Val307Ala (c.920T>C) is associated with Joubert syndrome, orofaciodigital syndrome I (ClinVar).

How common is OFD1 p.Val307Ala (c.920T>C) in the general population?

OFD1 p.Val307Ala (c.920T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OFD1 p.Val307Ala (c.920T>C)?

AlphaMissense predicts likely benign (score 0.1674) — an in-silico prediction, not a clinical call.

OFD1 p.Val307Ala

c.920T>C · VCV3755014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1674 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome

Computational evidence

Protein change
AlphaMissense	0.1674	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Val307Ala
Coding: c.920T>C
MANE Select: NM_003611
Type: single nucleotide variant
Location: chrX:13749518 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 307: a UniProt-annotated variant site (in jbts10; uncertain significance)

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.Val307Gly Uncertain significance ★ ⚠ same residue
OFD1 p.Val307Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
OFD1 p.Val307Leu 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

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-val307ala (accessed [today's date]).

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