Is RORB p.Glu6Gln (c.16G>C) pathogenic?

RORB p.Glu6Gln (c.16G>C) is classified Uncertain significance in RORB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). AlphaMissense: likely pathogenic (0.9651); Very rare (popmax 0.00167%, amr).

How common is RORB p.Glu6Gln (c.16G>C) in the general population?

RORB p.Glu6Gln (c.16G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about RORB p.Glu6Gln (c.16G>C)?

AlphaMissense predicts likely pathogenic (score 0.9651) — an in-silico prediction, not a clinical call.

RORB p.Glu6Gln

c.16G>C · rs1240476123 · VCV2874375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9651	likely pathogenic
REVEL	0.712	pathogenic-leaning
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 144 kb · p 1.9e-13 · regional, not allelic
Overall
CADD	32.0	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 E17Q vs ClinVar E6Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,992 alleles

Overall 6.2e-05% 1/1,612,988 alleles · very rare exomes 0/1,460,826 · genomes 1/152,162 · joint denominator

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: RORB
Protein: p.Glu6Gln
Coding: c.16G>C
MANE Select: NM_006914
dbSNP: rs1240476123
Type: single nucleotide variant
Location: chr9:74630290 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.48

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

Similar variants

RORB p.Glu6Gly Uncertain significance ★ ⚠ same residue
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

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-glu6gln (accessed [today's date]).

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