Is ODF2 p.Arg263Lys (c.788G>A) pathogenic?

ODF2 p.Arg263Lys (c.788G>A) is classified Likely pathogenic in ODF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-04). AlphaMissense: likely benign (0.3315); Rare (popmax 0.169%, sas); Associated with ODF2-related disorder.

What condition is associated with ODF2 p.Arg263Lys (c.788G>A)?

ODF2 p.Arg263Lys (c.788G>A) is associated with ODF2-related disorder (ClinVar).

How common is ODF2 p.Arg263Lys (c.788G>A) in the general population?

ODF2 p.Arg263Lys (c.788G>A) is rare (popmax 0.169%, sas) (gnomAD).

What do computational predictors say about ODF2 p.Arg263Lys (c.788G>A)?

AlphaMissense predicts likely benign (score 0.3315) — an in-silico prediction, not a clinical call.

ODF2 p.Arg263Lys

c.788G>A · VCV4682143

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3315 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.169%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ODF2-related disorder

Computational evidence

Protein change
AlphaMissense	0.3315	likely benign ⚠ discordant with ClinVar
REVEL	0.114	moderately benign-leaning
SaProt	LLR -6.23	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 12	GERP 6.2, phastCons 1
Overall
CADD	22.1	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 R180K vs ClinVar R263K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.169% South Asian · 154/90,952 alleles

Filtering AF 0.151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.149%

Overall 0.158% 2,545/1,613,508 alleles · rare exomes 2,327/1,461,286 · genomes 218/152,222 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.713%	140
Finnishnot grpmax-eligible	0.269%	372
South Asiangrpmax	0.169%	591
European (non-Finnish)	0.157%	637
Remaining individualsnot grpmax-eligible	0.144%	694
Admixed American	0.0701%	1,428
Middle Eastern	0.066%	1,515
African / African-American	0.024%	4,167
East Asian	0.00223%	44,802

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg263Lys
Coding: c.788G>A
MANE Select: NM_001351578
Type: single nucleotide variant
Location: chr9:128471426 (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

Disease context

ODF2-related disorder

Similar variants

ODF2 p.Thr793Ser Benign ★★ 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
ODF2 p.Ala518Pro 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-arg263lys (accessed [today's date]).

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