Is OGFOD1 p.Leu449Phe (c.1347A>T) pathogenic?

OGFOD1 p.Leu449Phe (c.1347A>T) is classified Uncertain significance in OGFOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely pathogenic (0.7058); Very rare (popmax 0.00833%, amr).

How common is OGFOD1 p.Leu449Phe (c.1347A>T) in the general population?

OGFOD1 p.Leu449Phe (c.1347A>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about OGFOD1 p.Leu449Phe (c.1347A>T)?

AlphaMissense predicts likely pathogenic (score 0.7058) — an in-silico prediction, not a clinical call.

OGFOD1 p.Leu449Phe

c.1347A>T · VCV3923944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7058 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7058	likely pathogenic
REVEL	0.365	indeterminate
SaProt	LLR -12.12	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2	GERP 0.58, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.11 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00833% Admixed American · 5/60,004 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000342% 5/1,461,194 alleles · very rare

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.Leu449Phe
Coding: c.1347A>T
MANE Select: NM_031885 · reported on NM_018233
Type: single nucleotide variant
Location: chr16:56474889 (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-leu449phe (accessed [today's date]).

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