AFAP1L2 p.Thr635=
c.1905C>G · rs144048981 · VCV2640863
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.709%, mid)
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 3 | GERP 0.38, phastCons 1 |
| Overall | ||
| CADD | 2.188 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.709%
Middle Eastern · 43/6,062 alleles
Filtering AF
0.558%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.553%
Overall
0.46%
7,431/1,614,124 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.709% | 141 |
| European (non-Finnish) | 0.569% | 176 |
| Remaining individualsnot grpmax-eligible | 0.392% | 255 |
| Admixed American | 0.285% | 351 |
| Ashkenazi Jewishnot grpmax-eligible | 0.165% | 604 |
| African / African-American | 0.131% | 766 |
| South Asian | 0.105% | 949 |
| Finnishnot grpmax-eligible | 0.0172% | 5,820 |
| East Asian | 0.00223% | 44,872 |
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
- AFAP1L2
- Protein
- p.Thr635=
- Coding
- c.1905C>G
- MANE Select
- NM_001001936
- dbSNP
- rs144048981
- Type
- single nucleotide variant
- Location
- chr10:114300246 (GRCh38)
- Gene constraint
- LOEUF 0.605 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.56 · 1 PDB
Similar variants
- AFAP1L2 p.Arg648His Uncertain significance ★★ ⚠ same type
- AFAP1L2 p.Arg730= Benign/Likely benign ★★ same type
- VWA2 p.Arg682Trp Benign ★★ ⚠ same type
- VWA2 p.Asn331= Benign ★★ same type
- VWA2 p.Gly641= Likely benign ★★ same type
- VWA2 p.His496Tyr Benign ★★ same type
- VWA2 p.Phe365= Benign ★★ same type
- VWA2 p.Pro544= 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/afap1l2-p-thr635 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown