AHNAK2 p.Ala3453=
c.10359G>A · VCV3845348
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0243%, afr)
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 -1.7 | GERP -0.66 |
| Overall | ||
| CADD | 0.355 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0243%
African / African-American · 18/74,062 alleles
Filtering AF
0.0156%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.013%
Overall
0.00596%
96/1,611,576 alleles · ultra-rare
exomes 79/1,461,360 · genomes 17/150,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0243% | 4,115 |
| Admixed American | 0.0134% | 7,478 |
| European (non-Finnish) | 0.00577% | 17,342 |
| South Asian | 0.0022% | 45,469 |
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
- AHNAK2
- Protein
- p.Ala3453=
- Coding
- c.10359G>A
- MANE Select
- NM_138420
- Type
- single nucleotide variant
- Location
- chr14:104945092 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
Similar variants
- AHNAK2 p.Ala3453Val Uncertain significance ★ ⚠ same residue
- AHNAK2 p.Glu3598Lys Uncertain significance ★★ ⚠ same type
- AHNAK2 p.Gly4376Ser Uncertain significance ★★ ⚠ same type
- AHNAK2 p.Lys2479Arg Uncertain significance ★★ ⚠ same type
- AHNAK2 p.Lys3309Asn Uncertain significance ★★ ⚠ same type
- AHNAK2 p.Val1351Met Uncertain significance ★★ ⚠ same type
- AHNAK2 p.Ala1115Val Benign/Likely benign ★★ same type
- AHNAK2 p.Ala1323Thr Likely 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/ahnak2-p-ala3453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown