Is OGFOD1 p.Pro399Ser (c.1195C>T) pathogenic?

OGFOD1 p.Pro399Ser (c.1195C>T) is classified Uncertain significance in OGFOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.0742); Very rare (popmax 0.00167%, amr).

How common is OGFOD1 p.Pro399Ser (c.1195C>T) in the general population?

OGFOD1 p.Pro399Ser (c.1195C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about OGFOD1 p.Pro399Ser (c.1195C>T)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

OGFOD1 p.Pro399Ser

c.1195C>T · VCV4560804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.25	GERP -0.58, phastCons 0.016
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.11 · regional, not allelic
Overall
CADD	8.312	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 0.00167% Admixed American · 1/60,004 alleles

Overall 6.2e-05% 1/1,614,056 alleles · very rare exomes 1/1,461,806 · genomes 0/152,250 · 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: OGFOD1
Protein: p.Pro399Ser
Coding: c.1195C>T
MANE Select: NM_018233
Type: single nucleotide variant
Location: chr16:56470701 (GRCh38)

Full OGFOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/ogfod1-p-pro399ser (accessed [today's date]).

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