Is RORB p.Ser37Arg (c.111C>G) pathogenic?

RORB p.Ser37Arg (c.111C>G) is classified Conflicting classifications of pathogenicity in RORB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-07). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RORB p.Ser37Arg (c.111C>G)?

RORB p.Ser37Arg (c.111C>G) is associated with Inborn genetic diseases (ClinVar).

How common is RORB p.Ser37Arg (c.111C>G) in the general population?

RORB p.Ser37Arg (c.111C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RORB p.Ser37Arg (c.111C>G)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

RORB p.Ser37Arg

c.111C>G · VCV3375773

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 9% in RORB
REVEL	0.927	moderately pathogenic-leaning
SaProt	LLR -14.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 144 kb · p 1.9e-13 · regional, not allelic
Overall
CADD	25.0	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 S48R vs ClinVar S37R) — 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: RORB
Protein: p.Ser37Arg
Coding: c.111C>G
MANE Select: NM_006914
Type: single nucleotide variant
Location: chr9:74634648 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.48
Residue 48 UniProt numbering: a DNA-binding region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RORB p.Ala95Thr Uncertain significance ★★ ⚠ same condition
RORB p.Arg214Gln Uncertain significance ★★ ⚠ same condition
RORB p.Asp337Glu Uncertain significance ★★ ⚠ same condition
RORB p.Gln107Arg Uncertain significance ★★ ⚠ same condition
RORB p.Ile147Thr Uncertain significance ★★ ⚠ same condition
RORB p.Ile183Val Uncertain significance ★★ ⚠ same condition
RORB p.Pro205Ser Likely benign ★★ same condition
RORB p.Cys10Ter Pathogenic ★ same condition

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-ser37arg (accessed [today's date]).

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