Is OFD1 p.Pro671Ser (c.2011C>T) pathogenic?

OFD1 p.Pro671Ser (c.2011C>T) is classified Uncertain significance in OFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely benign (0.0792); Very rare (popmax 0.00199%, sas); Associated with Joubert syndrome.

What condition is associated with OFD1 p.Pro671Ser (c.2011C>T)?

OFD1 p.Pro671Ser (c.2011C>T) is associated with Joubert syndrome, orofaciodigital syndrome I (ClinVar).

How common is OFD1 p.Pro671Ser (c.2011C>T) in the general population?

OFD1 p.Pro671Ser (c.2011C>T) is very rare (popmax 0.00199%, sas) (gnomAD).

What do computational predictors say about OFD1 p.Pro671Ser (c.2011C>T)?

AlphaMissense predicts likely benign (score 0.0792) — an in-silico prediction, not a clinical call.

OFD1 p.Pro671Ser

c.2011C>T · rs2147048847 · VCV2079869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00199%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome

Computational evidence

Protein change
AlphaMissense	0.0792	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -4.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.087	GERP -0.25
Regional constraint	o/e 1.02	unconstrained · MANE · 8,639 bp · p 0.77 · regional, not allelic
Overall
CADD	0.596	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

Grpmax group 0.00199% South Asian · 1/50,375 alleles

Overall 8.51e-05% 1/1,174,731 alleles · very rare exomes 1/1,060,955 · genomes 0/113,776 · joint denominator

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.Pro671Ser
Coding: c.2011C>T
MANE Select: NM_003611
dbSNP: rs2147048847
Type: single nucleotide variant
Location: chrX:13760471 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 671: the 'mediates the interaction with sdccag8' 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.Pro671del Uncertain significance ★★ same residue
OFD1 p.Pro671Leu 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-pro671ser (accessed [today's date]).

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