Is OFD1 p.Arg799Pro (c.2396G>C) pathogenic?

OFD1 p.Arg799Pro (c.2396G>C) is classified Uncertain significance in OFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1118); Absent from gnomAD v4.1.

How common is OFD1 p.Arg799Pro (c.2396G>C) in the general population?

OFD1 p.Arg799Pro (c.2396G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OFD1 p.Arg799Pro (c.2396G>C)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

OFD1 p.Arg799Pro

c.2396G>C · VCV4823517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -6.66	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 0.72	GERP 3
Regional constraint	o/e 1.02	unconstrained · MANE · 8,639 bp · p 0.77 · regional, not allelic
Overall
CADD	4.772	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

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.Arg799Pro
Coding: c.2396G>C
MANE Select: NM_003611
Type: single nucleotide variant
Location: chrX:13762352 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 799: the 'mediates the interaction with sdccag8' region

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

Similar variants

OFD1 p.Arg799Ter Pathogenic ★ same residue
OFD1 p.Arg799Gln Uncertain significance ★ ⚠ same residue
OFD1 c.1411+1G>A Pathogenic ★★ same type
OFD1 c.2600-1G>C Pathogenic/Likely pathogenic ★★ same type
OFD1 c.655-8A>G Likely pathogenic ★★ same type
OFD1 p.Arg367Ter Pathogenic ★★ same type
OFD1 p.Arg41Ter Pathogenic ★★ same type
OFD1 p.Arg890Ter Pathogenic/Likely pathogenic ★★ same type

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-arg799pro (accessed [today's date]).

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