NCOA4 p.Pro508=
c.1524C>G · rs79761167 · VCV715258
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.41%, eas)
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 1.7 | GERP 0.21, phastCons 0.99 |
| Overall | ||
| CADD | 4.161 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.41%
East Asian · 632/44,886 alleles
Filtering AF
1.32%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.28%
Overall
0.206%
3,320/1,614,112 alleles · low-frequency
exomes 3,019/1,461,880 · genomes 301/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.41% | 71 |
| Admixed American | 0.921% | 109 |
| South Asian | 0.644% | 155 |
| Remaining individualsnot grpmax-eligible | 0.376% | 266 |
| European (non-Finnish) | 0.109% | 920 |
| Middle Eastern | 0.066% | 1,514 |
| African / African-American | 0.036% | 2,778 |
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
- NCOA4
- Protein
- p.Pro508=
- Coding
- c.1524C>G
- MANE Select
- NM_001145263
- dbSNP
- rs79761167
- Type
- single nucleotide variant
- Location
- chr10:46010397 (GRCh38)
- Gene constraint
- LOEUF 0.65 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 56.41 · 3 PDB
- Residue 508
- the 'interaction with ferritin heavy chain fth1' region; the 'disordered' region
Similar variants
- NCOA4 p.Ala483Thr Benign ★★ same type
- NCOA4 p.Asn248Ser Benign ★★ same type
- NCOA4 p.Gly441Glu Benign ★★ ⚠ same type
- NCOA4 p.Ser495Leu Benign ★★ same type
- NCOA4 p.Thr229Ile Benign/Likely benign ★★ same type
- NCOA4 c.1839+200C>T Uncertain significance ★ same type
- NCOA4 c.1839+208A>G Uncertain significance ★ same type
- NCOA4 c.1839+209A>G 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/ncoa4-p-pro508 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown