Is ODF2 p.Arg231Cys (c.691C>T) pathogenic?

ODF2 p.Arg231Cys (c.691C>T) is classified Uncertain significance in ODF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-11). AlphaMissense: likely benign (0.1509); Very rare (popmax 0.00221%, sas).

How common is ODF2 p.Arg231Cys (c.691C>T) in the general population?

ODF2 p.Arg231Cys (c.691C>T) is very rare (popmax 0.00221%, sas) (gnomAD).

What do computational predictors say about ODF2 p.Arg231Cys (c.691C>T)?

AlphaMissense predicts likely benign (score 0.1509) — an in-silico prediction, not a clinical call.

ODF2 p.Arg231Cys

c.691C>T · VCV3882595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1509 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1509	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -5.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 5.5, phastCons 1
Overall
CADD	28.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R148C vs ClinVar R231C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% South Asian · 2/90,458 alleles

Filtering AF 0.000367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000435% 7/1,610,632 alleles · very rare exomes 7/1,458,370 · genomes 0/152,262 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00221%	45,229
European (non-Finnish)	0.000424%	235,745

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.Arg231Cys
Coding: c.691C>T
MANE Select: NM_001351578
Type: single nucleotide variant
Location: chr9:128471329 (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.Arg231Gly Uncertain significance ★ ⚠ same residue
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

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-arg231cys (accessed [today's date]).

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