Is RORA p.Ala7Val (c.20C>T) pathogenic?

RORA p.Ala7Val (c.20C>T) is classified Uncertain significance in RORA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.1188); Very rare (popmax 0.00401%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RORA p.Ala7Val (c.20C>T)?

RORA p.Ala7Val (c.20C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RORA p.Ala7Val (c.20C>T) in the general population?

RORA p.Ala7Val (c.20C>T) is very rare (popmax 0.00401%, nfe) (gnomAD).

What do computational predictors say about RORA p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely benign (score 0.1188) — an in-silico prediction, not a clinical call.

RORA p.Ala7Val

c.20C>T · rs747354303 · VCV3155738

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1188	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 551 kb · p 0.0056 · regional, not allelic
Overall
CADD	22.5	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% European (non-Finnish) · 46/1,147,828 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00331% 51/1,542,634 alleles · very rare exomes 47/1,394,252 · genomes 4/148,382 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00401%	24,953
Remaining individualsnot grpmax-eligible	0.00336%	29,797
African / African-American	0.0028%	35,697
South Asian	0.00121%	82,860

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: RORA
Protein: p.Ala7Val
Coding: c.20C>T
MANE Select: NM_134261
dbSNP: rs747354303
Type: single nucleotide variant
Location: chr15:61229199 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB
Residue 7: the 'disordered' region

Full RORA 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

RORA p.Ala7Ser Uncertain significance ★★ ⚠ same residue
RORA p.Arg462Ter Pathogenic/Likely pathogenic ★★ same condition
RORA p.Gln278His Uncertain significance ★★ ⚠ same condition
RORA p.Gly211Arg Uncertain significance ★★ ⚠ same condition
RORA p.Lys151Gln Uncertain significance ★★ ⚠ same condition
RORA p.Thr328Arg Uncertain significance ★★ ⚠ same condition
RORA c.197-26379G>A Likely benign ★★ same condition
RORA p.Asp21Gly 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/rora-p-ala7val (accessed [today's date]).

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