SRCAP p.Lys664=
c.1992A>G · rs140349444 · VCV2148929
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0082%, nfe)
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 9.3 | GERP 2.7, phastCons 1 |
| Overall | ||
| CADD | 17.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0082%
European (non-Finnish) · 95/1,159,192 alleles
Filtering AF
0.00684%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00636%
Overall
0.00625%
98/1,567,962 alleles · very rare
exomes 86/1,415,802 · genomes 12/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0082% | 12,202 |
| Remaining individualsnot grpmax-eligible | 0.00332% | 30,148 |
| Admixed American | 0.00196% | 51,040 |
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
- SRCAP
- Protein
- p.Lys664=
- Coding
- c.1992A>G
- MANE Select
- NM_006662
- dbSNP
- rs140349444
- Type
- single nucleotide variant
- Location
- chr16:30712438 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 664
- the helicase atp-binding domain; a UniProt-annotated variant site (in dehmba); a β-strand
Similar variants
- SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same type
- SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same type
- SRCAP p.Arg2444Ter Pathogenic ★★ same type
- SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same type
- SRCAP p.Arg2748Ter Pathogenic ★★ same type
- SRCAP p.Gln2407Ter Pathogenic ★★ same type
- SRCAP p.Gln2419Ter Pathogenic ★★ same type
- SRCAP p.Gln2665Ter Pathogenic/Likely pathogenic ★★ 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/srcap-p-lys664 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown