Is RORB p.Ile413Met (c.1239A>G) pathogenic?

RORB p.Ile413Met (c.1239A>G) is classified Uncertain significance in RORB (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-16). AlphaMissense: likely benign (0.1686); No allele count reported in gnomAD v4.1 (AN 1,611,214).

How common is RORB p.Ile413Met (c.1239A>G) in the general population?

RORB p.Ile413Met (c.1239A>G) is no allele count reported in gnomAD v4.1 (AN 1,611,214) (gnomAD).

What do computational predictors say about RORB p.Ile413Met (c.1239A>G)?

AlphaMissense predicts likely benign (score 0.1686) — an in-silico prediction, not a clinical call.

RORB p.Ile413Met

c.1239A>G · VCV4903365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1686 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,214)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1686	likely benign
REVEL	0.452	indeterminate
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -5.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 20 kb · p 2.1e-06 · regional, not allelic
Overall
CADD	22.0	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 I424M vs ClinVar I413M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,214). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RORB
Protein: p.Ile413Met
Coding: c.1239A>G
MANE Select: NM_006914
Type: single nucleotide variant
Location: chr9:74685477 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.48
Residue 424 UniProt numbering: the nr lbd domain; a UniProt-annotated variant site (in eig15; loss of subcellular location in the nucleoplasm)

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

Similar variants

RORB c.94-1G>A Pathogenic/Likely pathogenic ★★ same type
RORB p.Arg214Ter Pathogenic/Likely pathogenic ★★ same type
RORB p.Arg372Ter Pathogenic ★★ same type
RORB p.Arg66Ter Pathogenic/Likely pathogenic ★★ same type
RORB p.Ala269Thr Uncertain significance ★★ ⚠ same type
RORB p.Ala95Thr Uncertain significance ★★ ⚠ same type
RORB p.Arg214Gln Uncertain significance ★★ ⚠ same type
RORB p.Arg279Trp 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/rorb-p-ile413met (accessed [today's date]).

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