Is NCOA1 p.Pro445= (c.1335C>T) pathogenic?

NCOA1 p.Pro445= (c.1335C>T) is classified Likely benign in NCOA1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-03-04). Ultra-rare (popmax 0.0329%, mid); Associated with NCOA1-related disorder.

What condition is associated with NCOA1 p.Pro445= (c.1335C>T)?

NCOA1 p.Pro445= (c.1335C>T) is associated with NCOA1-related disorder (ClinVar).

How common is NCOA1 p.Pro445= (c.1335C>T) in the general population?

NCOA1 p.Pro445= (c.1335C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

NCOA1 p.Pro445=

c.1335C>T · rs369622360 · VCV3034591

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

NCOA1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.94	GERP -1.1, phastCons 1
Overall
CADD	11.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00452% 73/1,614,030 alleles · ultra-rare exomes 61/1,461,882 · genomes 12/152,148 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
Admixed American	0.0217%	4,615
Remaining individualsnot grpmax-eligible	0.0128%	7,810
African / African-American	0.0107%	9,362
European (non-Finnish)	0.00347%	28,781
South Asian	0.0011%	91,078

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: NCOA1
Protein: p.Pro445=
Coding: c.1335C>T
MANE Select: NM_003743
dbSNP: rs369622360
Type: single nucleotide variant
Location: chr2:24706805 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 47.53 · 304 PDB
Residue 445: the 'interaction with stat3' region

Full NCOA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NCOA1-related disorder

Similar variants

NCOA1 p.Gly439Glu Uncertain significance ★★ ⚠ same condition
NCOA1 p.Ser1139Asn Uncertain significance ★★ ⚠ same condition
NCOA1 p.Arg1091Ser Uncertain significance ★ ⚠ same condition
NCOA1 p.Asp6Gly Uncertain significance ★ ⚠ same condition
NCOA1 p.Asp914Glu Uncertain significance ★ ⚠ same condition
NCOA1 p.Glu822Lys Uncertain significance ★ ⚠ same condition
NCOA1 c.3881+5G>A Uncertain significance same condition
NCOA1 c.4156-139A>C Uncertain significance 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/ncoa1-p-pro445 (accessed [today's date]).

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