Is ODF2 p.Ile685Phe (c.2053A>T) pathogenic?

ODF2 p.Ile685Phe (c.2053A>T) is classified Uncertain significance in ODF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-31). AlphaMissense: ambiguous (0.5231); Absent from gnomAD v4.1.

How common is ODF2 p.Ile685Phe (c.2053A>T) in the general population?

ODF2 p.Ile685Phe (c.2053A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ODF2 p.Ile685Phe (c.2053A>T)?

AlphaMissense predicts ambiguous (score 0.5231) — an in-silico prediction, not a clinical call.

ODF2 p.Ile685Phe

c.2053A>T · VCV3302177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5231 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5231	ambiguous
REVEL	0.248	benign-leaning
SaProt	LLR -6.20	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I602F vs ClinVar I685F) — verify the residue.

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: ODF2
Protein: p.Ile685Phe
Coding: c.2053A>T
MANE Select: NM_001351578
Type: single nucleotide variant
Location: chr9:128494561 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.64
Residue 602 UniProt numbering: the 'interaction with bbof1' region

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-ile685phe (accessed [today's date]).

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