Is OFD1 p.Ser461Arg (c.1383T>A) pathogenic?

OFD1 p.Ser461Arg (c.1383T>A) is classified Uncertain significance in OFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-02). AlphaMissense: ambiguous (0.3405); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with OFD1 p.Ser461Arg (c.1383T>A)?

OFD1 p.Ser461Arg (c.1383T>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is OFD1 p.Ser461Arg (c.1383T>A) in the general population?

OFD1 p.Ser461Arg (c.1383T>A) is absent from gnomAD v4.1 (gnomAD).

How is Primary ciliary dyskinesia 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.Ser461Arg (c.1383T>A)?

AlphaMissense predicts ambiguous (score 0.3405) — an in-silico prediction, not a clinical call.

OFD1 p.Ser461Arg

c.1383T>A · VCV4840776

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3405 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.3405	ambiguous
REVEL	0.397	indeterminate
SaProt	LLR -9.55	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.66	GERP -1.8
Regional constraint	o/e 0.93	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	14.33	PHRED · no single calibrated threshold — expert panels disagree

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.Ser461Arg
Coding: c.1383T>A
MANE Select: NM_003611
Type: single nucleotide variant
Location: chrX:13756739 (GRCh38)
Structure: AlphaFold pLDDT 68.41

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

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

OFD1 p.Arg909Ter Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Ala213Gly Uncertain significance ★★ ⚠ same condition
OFD1 p.Ala506Gly Uncertain significance ★★ ⚠ same condition
OFD1 p.Ala856Val Uncertain significance ★★ ⚠ same condition
OFD1 p.Arg263Trp Uncertain significance ★★ ⚠ same condition
OFD1 p.Arg467Ser Uncertain significance ★★ ⚠ same condition
OFD1 p.Arg487Trp Uncertain significance ★★ ⚠ same condition
OFD1 p.Asn118Thr 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-ser461arg (accessed [today's date]).

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