Is OFD1 p.Ser92= (c.276T>C) pathogenic?

OFD1 p.Ser92= (c.276T>C) is classified Conflicting classifications of pathogenicity in OFD1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-01). Rare (popmax 0.114%, afr); Associated with orofaciodigital syndrome I.

What condition is associated with OFD1 p.Ser92= (c.276T>C)?

OFD1 p.Ser92= (c.276T>C) is associated with orofaciodigital syndrome I, primary ciliary dyskinesia, Joubert syndrome (ClinVar).

How common is OFD1 p.Ser92= (c.276T>C) in the general population?

OFD1 p.Ser92= (c.276T>C) is rare (popmax 0.114%, afr) (gnomAD).

OFD1 p.Ser92=

c.276T>C · rs201675886 · VCV288538

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.114%, afr)

Conditions

orofaciodigital syndrome I

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 0.06	GERP -0.081, phastCons 0.97
Overall
CADD	11.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.114% African / African-American · 65/57,032 alleles

Filtering AF 0.0917% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0836%

Overall 0.00645% 78/1,208,455 alleles · rare exomes 44/1,097,100 · genomes 34/111,355 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.114%	877
Middle Eastern	0.0231%	4,328
Admixed American	0.0153%	6,529
Remaining individualsnot grpmax-eligible	0.0105%	9,513

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.Ser92=
Coding: c.276T>C
MANE Select: NM_003611
dbSNP: rs201675886
Type: single nucleotide variant
Location: chrX:13736642 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 92: the lish domain

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: primary ciliary dyskinesia Joubert syndrome

Similar variants

OFD1 p.Ser92Phe Uncertain significance ★ ⚠ same residue
OFD1 p.Ser92Pro Likely pathogenic ★ same residue
TRAPPC2 p.Glu92Asp 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-ser92 (accessed [today's date]).

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