Is OFD1 p.Gln331Ter (c.991C>T) pathogenic?

OFD1 p.Gln331Ter (c.991C>T) is classified Conflicting classifications of pathogenicity in OFD1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-17). No allele count reported in gnomAD v4.1 (AN 1,202,213); Associated with Joubert syndrome 10.

What condition is associated with OFD1 p.Gln331Ter (c.991C>T)?

OFD1 p.Gln331Ter (c.991C>T) is associated with Joubert syndrome 10 (ClinVar).

How common is OFD1 p.Gln331Ter (c.991C>T) in the general population?

OFD1 p.Gln331Ter (c.991C>T) is no allele count reported in gnomAD v4.1 (AN 1,202,213) (gnomAD).

OFD1 p.Gln331Ter

c.991C>T · rs1555904005 · VCV488753

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,202,213)

Conditions

Joubert syndrome 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 23
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.49	GERP -2.6, phastCons 0.011
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,202,213). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OFD1
Protein: p.Gln331Ter
Coding: c.991C>T
MANE Select: NM_003611
dbSNP: rs1555904005
Type: single nucleotide variant
Location: chrX:13751304 (GRCh38)
Structure: AlphaFold pLDDT 68.41

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

Disease context

Joubert syndrome 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OFD1 c.1411+1G>A Pathogenic ★★ same condition
OFD1 p.Arg41Ter Pathogenic ★★ same condition
OFD1 p.Arg890Ter Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Gln966Ter Pathogenic/Likely pathogenic ★★ same condition
OFD1 c.2600-3T>C Uncertain significance ★★ same condition
OFD1 c.935+4A>G Uncertain significance ★★ same condition
OFD1 p.Ala530Gly Uncertain significance ★★ ⚠ same condition
OFD1 p.Ala648Ser Uncertain significance ★★ ⚠ 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-gln331ter (accessed [today's date]).

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