Is RORB p.Leu170Val (c.508C>G) pathogenic?

RORB p.Leu170Val (c.508C>G) is classified Conflicting classifications of pathogenicity in RORB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-07). AlphaMissense: likely benign (0.0864); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RORB p.Leu170Val (c.508C>G)?

RORB p.Leu170Val (c.508C>G) is associated with Inborn genetic diseases (ClinVar).

How common is RORB p.Leu170Val (c.508C>G) in the general population?

RORB p.Leu170Val (c.508C>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about RORB p.Leu170Val (c.508C>G)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

RORB p.Leu170Val

c.508C>G · rs759595738 · VCV1439310

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.34	indeterminate
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 18 kb · p 0.076 · regional, not allelic
Overall
CADD	23.7	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 L181V vs ClinVar L170V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,030 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,052 alleles · very rare exomes 4/1,461,882 · genomes 1/152,170 · 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.Leu170Val
Coding: c.508C>G
MANE Select: NM_006914
dbSNP: rs759595738
Type: single nucleotide variant
Location: chr9:74642686 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.48
Residue 181 UniProt numbering: 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

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-leu170val (accessed [today's date]).

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