NRCAM p.Pro975=
c.2925G>A · rs143805055 · VCV3044128
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.38%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.8 | GERP -4.4 |
| Overall | ||
| CADD | 2.621 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.38%
Middle Eastern · 23/6,056 alleles
Filtering AF
0.26%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.22%
Overall
0.0259%
418/1,613,514 alleles · rare
exomes 335/1,461,302 · genomes 83/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.38% | 263 |
| Admixed American | 0.145% | 690 |
| Remaining individualsnot grpmax-eligible | 0.0464% | 2,154 |
| South Asian | 0.0374% | 2,676 |
| European (non-Finnish) | 0.0195% | 5,129 |
| African / African-American | 0.016% | 6,251 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,584 |
| Finnishnot grpmax-eligible | 0.00313% | 31,987 |
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
- NRCAM
- Protein
- p.Pro975=
- Coding
- c.2925G>A
- MANE Select
- NM_001037132
- dbSNP
- rs143805055
- Type
- single nucleotide variant
- Location
- chr7:108178039 (GRCh38)
- Gene constraint
- LOEUF 0.652 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.85 · 2 PDB
- Residue 975
- the fibronectin type-iii 4 domain; a UniProt-annotated variant site (in nednms)
Similar variants
- NRCAM p.Gly1261Glu Uncertain significance ★★ ⚠ same type
- NRCAM p.Lys902Thr Uncertain significance ★★ ⚠ same type
- NRCAM p.Pro74Leu Uncertain significance ★★ ⚠ same type
- NRCAM p.Ser909Asn Uncertain significance ★★ ⚠ same type
- NRCAM c.1631-9A>G Benign ★★ same type
- NRCAM c.2531-15C>T Benign ★★ same type
- NRCAM p.Ala1285Thr Benign ★★ same type
- NRCAM p.Ala534= 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/nrcam-p-pro975 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown