AHNAK2 p.Pro4491=
c.13473A>G · rs28600075 · VCV1261767
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 67%, mid) — too common for a highly-penetrant pathogenic allele
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 -12 | GERP -1.8 |
| Overall | ||
| CADD | 0.087 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
67%
Middle Eastern · 4,057/6,058 alleles
Filtering AF
65.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 64.5%
Overall
54.2%
874,841/1,612,960 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 67% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 65.4% | 2 |
| African / African-American | 64.7% | 2 |
| South Asian | 62% | 2 |
| Remaining individualsnot grpmax-eligible | 56.1% | 2 |
| European (non-Finnish) | 54% | 2 |
| Admixed American | 50.8% | 2 |
| Amishnot grpmax-eligible | 46.5% | 2 |
| East Asian | 40.9% | 2 |
| Finnishnot grpmax-eligible | 40.6% | 2 |
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.Pro4491=
- Coding
- c.13473A>G
- MANE Select
- NM_138420
- dbSNP
- rs28600075
- Type
- single nucleotide variant
- Location
- chr14:104941978 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
Similar variants
- 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
- AHNAK2 p.Ala1818Thr Benign/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-pro4491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown