Is RORC p.Ala93Val (c.278C>T) pathogenic?

RORC p.Ala93Val (c.278C>T) is classified Uncertain significance in RORC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.1409); Ultra-rare (popmax 0.0101%, sas).

How common is RORC p.Ala93Val (c.278C>T) in the general population?

RORC p.Ala93Val (c.278C>T) is ultra-rare (popmax 0.0101%, sas) (gnomAD).

What do computational predictors say about RORC p.Ala93Val (c.278C>T)?

AlphaMissense predicts likely benign (score 0.1409) — an in-silico prediction, not a clinical call.

RORC p.Ala93Val

c.278C>T · VCV4911066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1409 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1409	likely benign
REVEL	0.738	pathogenic-leaning
SaProt	LLR -8.55	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 2,118 bp · p 0.0015 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0101% South Asian · 9/89,334 alleles

Filtering AF 0.00523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00392%

Overall 0.00125% 20/1,605,900 alleles · ultra-rare exomes 19/1,453,568 · genomes 1/152,332 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0101%	9,926
Remaining individualsnot grpmax-eligible	0.00322%	31,086
East Asian	0.00225%	44,538
African / African-American	0.00133%	74,970
European (non-Finnish)	0.000595%	168,075

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: RORC
Protein: p.Ala93Val
Coding: c.278C>T
MANE Select: NM_005060
Type: single nucleotide variant
Location: chr1:151816684 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 162 PDB
Residue 93: a DNA-binding region

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

Similar variants

RORC p.Ala93= Likely benign ★ same residue
RORC p.Arg10Gln Uncertain significance ★★ ⚠ same type
RORC p.Arg13Trp Uncertain significance ★★ ⚠ same type
RORC p.Arg208Gln Uncertain significance ★★ ⚠ same type
RORC p.Arg237Ser Uncertain significance ★★ ⚠ same type
RORC p.Arg257His Uncertain significance ★★ ⚠ same type
RORC p.Arg288Gln Uncertain significance ★★ ⚠ same type
RORC p.Arg82Gln 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/rorc-p-ala93val (accessed [today's date]).

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