Is NCOR1 p.Pro613Leu (c.1838C>T) pathogenic?

NCOR1 p.Pro613Leu (c.1838C>T) is classified Uncertain significance in NCOR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-07). AlphaMissense: likely benign (0.1388); Very rare (popmax 0.00892%, eas).

How common is NCOR1 p.Pro613Leu (c.1838C>T) in the general population?

NCOR1 p.Pro613Leu (c.1838C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about NCOR1 p.Pro613Leu (c.1838C>T)?

AlphaMissense predicts likely benign (score 0.1388) — an in-silico prediction, not a clinical call.

NCOR1 p.Pro613Leu

c.1838C>T · rs148932674 · VCV2570260

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1388	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -8.75	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 5,139 bp · p 0.025 · regional, not allelic
Overall
CADD	29.4	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 0.00892% East Asian · 4/44,860 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00279% 45/1,613,280 alleles · very rare exomes 41/1,460,970 · genomes 4/152,310 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,215
Admixed American	0.00834%	11,992
Finnishnot grpmax-eligible	0.00781%	12,803
Remaining individualsnot grpmax-eligible	0.0032%	31,230
European (non-Finnish)	0.00237%	42,125
South Asian	0.0011%	90,958

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: NCOR1
Protein: p.Pro613Leu
Coding: c.1838C>T
MANE Select: NM_006311
dbSNP: rs148932674
Type: single nucleotide variant
Location: chr17:16121066 (GRCh38)
Gene constraint: LOEUF 0.292 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.40 · 27 PDB
Residue 613: the 'disordered' region

Full NCOR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NCOR1 p.Ala2182Thr Benign ★★ same type
NCOR1 p.Arg2132= Benign ★★ same type
NCOR1 p.Arg856= Likely benign ★★ same type
NCOR1 p.Gln1621= Benign ★★ same type
NCOR1 p.Gly1348= Benign ★★ same type
NCOR1 p.Gly838Ala Benign/Likely benign ★★ same type
NCOR1 p.Ile2055= Benign/Likely benign ★★ same type
NCOR1 p.Leu1406Phe Benign ★★ ⚠ 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/ncor1-p-pro613leu (accessed [today's date]).

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