SHANK3 p.Phe142=
c.426C>T · VCV4849034
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00953%, sas)
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 2.4 | GERP 0.031, phastCons 1 |
| Overall | ||
| CADD | 18.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00953%
South Asian · 8/83,986 alleles
Filtering AF
0.00469%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00345%
Overall
0.000711%
11/1,547,968 alleles · very rare
exomes 9/1,395,776 · genomes 2/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00953% | 10,498 |
| Remaining individualsnot grpmax-eligible | 0.00334% | 29,947 |
| East Asian | 0.00244% | 40,924 |
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
- SHANK3
- Protein
- p.Phe142=
- Coding
- c.426C>T
- MANE Select
- NM_001372044
- Type
- single nucleotide variant
- Location
- chr22:50675185 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.36 · 3 PDB
- Residue 142
- the 'intramolecular interaction with the ank repeats' region
Similar variants
- SHANK3 c.2455+1G>A Pathogenic ★★ same type
- SHANK3 c.2455+1G>C Pathogenic/Likely pathogenic ★★ same type
- SHANK3 c.2838C>G Pathogenic ★★ same type
- SHANK3 p.Arg166Ter Pathogenic/Likely pathogenic ★★ same type
- SHANK3 p.Arg1733Ter Pathogenic/Likely pathogenic ★★ same type
- SHANK3 p.Arg432Ter Pathogenic ★★ same type
- SHANK3 p.Asp1564Tyr Pathogenic ★★ same type
- SHANK3 p.Gln1364Ter 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/shank3-p-phe142 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown