Is RORB p.Ala238Val (c.713C>T) pathogenic?

RORB p.Ala238Val (c.713C>T) is classified Conflicting classifications of pathogenicity in RORB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-27). AlphaMissense: likely benign (0.1312); Very rare (popmax 0.00754%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RORB p.Ala238Val (c.713C>T)?

RORB p.Ala238Val (c.713C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RORB p.Ala238Val (c.713C>T) in the general population?

RORB p.Ala238Val (c.713C>T) is very rare (popmax 0.00754%, nfe) (gnomAD).

What do computational predictors say about RORB p.Ala238Val (c.713C>T)?

AlphaMissense predicts likely benign (score 0.1312) — an in-silico prediction, not a clinical call.

RORB p.Ala238Val

c.713C>T · rs145736840 · VCV1449560

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1312 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00754%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1312	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 4,905 bp · p 1.1e-12 · regional, not allelic
Overall
CADD	24.0	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 A249V vs ClinVar A238V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00754% European (non-Finnish) · 89/1,179,734 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00614% 99/1,613,654 alleles · very rare exomes 97/1,461,396 · genomes 2/152,258 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00754%	13,255
Remaining individualsnot grpmax-eligible	0.0064%	15,624
South Asian	0.00439%	22,756
Admixed American	0.00167%	59,948
African / African-American	0.00133%	75,028

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.Ala238Val
Coding: c.713C>T
MANE Select: NM_006914
dbSNP: rs145736840
Type: single nucleotide variant
Location: chr9:74660692 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.48
Residue 249 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

Disease context

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

Similar variants

RORB p.Ala238= Benign/Likely benign ★★ same residue
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

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-ala238val (accessed [today's date]).

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