Is ODF2 p.Pro97Arg (c.290C>G) pathogenic?

ODF2 p.Pro97Arg (c.290C>G) is classified Uncertain significance in ODF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). Very rare (popmax 0.000339%, nfe).

How common is ODF2 p.Pro97Arg (c.290C>G) in the general population?

ODF2 p.Pro97Arg (c.290C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

ODF2 p.Pro97Arg

c.290C>G · VCV4560765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.513	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 6.6, phastCons 1
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,998 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,008 alleles · very rare exomes 4/1,461,730 · genomes 0/152,278 · 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: ODF2
Protein: p.Pro97Arg
Coding: c.290C>G
MANE Select: NM_001351578
Type: single nucleotide variant
Location: chr9:128460584 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.64

Full ODF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ODF2 p.Thr793Ser Benign ★★ same type
ODF2 p.Arg263Lys Likely pathogenic ★ ⚠ same type
ODF2 p.Ala120Val Uncertain significance ★ same type
ODF2 p.Ala216Val Uncertain significance ★ ⚠ same type
ODF2 p.Ala297Val Uncertain significance ★ ⚠ same type
ODF2 p.Ala302Val Uncertain significance ★ ⚠ same type
ODF2 p.Ala310Thr Uncertain significance ★ ⚠ same type
ODF2 p.Ala441Ser Uncertain significance ★ ⚠ 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/odf2-p-pro97arg (accessed [today's date]).

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