Is RCOR3 p.Pro293Ser (c.877C>T) pathogenic?

RCOR3 p.Pro293Ser (c.877C>T) is classified Uncertain significance in RCOR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.1212); Ultra-rare (popmax 0.0329%, mid).

How common is RCOR3 p.Pro293Ser (c.877C>T) in the general population?

RCOR3 p.Pro293Ser (c.877C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about RCOR3 p.Pro293Ser (c.877C>T)?

AlphaMissense predicts likely benign (score 0.1212) — an in-silico prediction, not a clinical call.

RCOR3 p.Pro293Ser

c.877C>T · VCV4576857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1212 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1212	likely benign
REVEL	0.5	indeterminate
SaProt	LLR -6.98	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 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 54 kb · p 4.9e-18 · regional, not allelic
Overall
CADD	21.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P235S vs ClinVar P293S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000991% 16/1,613,970 alleles · ultra-rare exomes 15/1,461,864 · genomes 1/152,106 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
African / African-American	0.0134%	7,489
Remaining individualsnot grpmax-eligible	0.0064%	15,622

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: RCOR3
Protein: p.Pro293Ser
Coding: c.877C>T
MANE Select: NM_001136223
Type: single nucleotide variant
Location: chr1:211289334 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.28 · 1 PDB
Residue 235 UniProt numbering: a β-strand

Full RCOR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RCOR3 p.Ala158Gly Uncertain significance ★ same type
RCOR3 p.Ala18Val Uncertain significance ★ same type
RCOR3 p.Ala22Thr Uncertain significance ★ same type
RCOR3 p.Ala455Ser Uncertain significance ★ ⚠ same type
RCOR3 p.Ala517Thr Uncertain significance ★ ⚠ same type
RCOR3 p.Ala63Gly Uncertain significance ★ ⚠ same type
RCOR3 p.Arg203Cys Uncertain significance ★ ⚠ same type
RCOR3 p.Arg274Cys 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/rcor3-p-pro293ser (accessed [today's date]).

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