Is OFD1 p.Ile784Ser (c.2351T>G) pathogenic?

OFD1 p.Ile784Ser (c.2351T>G) is classified Uncertain significance in OFD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-11). AlphaMissense: likely benign (0.0962); Very rare (popmax 0.00217%, amr); Associated with retinitis pigmentosa 23.

What condition is associated with OFD1 p.Ile784Ser (c.2351T>G)?

OFD1 p.Ile784Ser (c.2351T>G) is associated with retinitis pigmentosa 23, Simpson-Golabi-Behmel syndrome type 2, Joubert syndrome 10 (ClinVar).

How common is OFD1 p.Ile784Ser (c.2351T>G) in the general population?

OFD1 p.Ile784Ser (c.2351T>G) is very rare (popmax 0.00217%, amr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about OFD1 p.Ile784Ser (c.2351T>G)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

OFD1 p.Ile784Ser

c.2351T>G · rs2047912842 · VCV1328774

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 23

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -3.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.86	GERP -13
Regional constraint	o/e 1.02	unconstrained · MANE · 8,639 bp · p 0.77 · regional, not allelic
Overall
CADD	0.011	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 0.00217% Admixed American · 1/46,017 alleles

Overall 0.000248% 3/1,210,953 alleles · very rare exomes 3/1,097,571 · genomes 0/113,382 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00217%	46,017
South Asian	0.00176%	56,952
European (non-Finnish)	0.000112%	894,879

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.Ile784Ser
Coding: c.2351T>G
MANE Select: NM_003611
dbSNP: rs2047912842
Type: single nucleotide variant
Location: chrX:13761175 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 784: 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

retinitis pigmentosa 23 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Simpson-Golabi-Behmel syndrome type 2 Joubert syndrome 10 orofaciodigital syndrome I

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

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.Gln966Ter 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-ile784ser (accessed [today's date]).

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