AHNAK2 p.Cys1872Ser
c.5614T>A · rs181708085 · VCV2644785
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0531 | likely benign |
|---|---|---|
| REVEL | 0.008 | strongly benign-leaning |
| SaProt | — | not scored · why |
| ⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -7.3 | GERP -0.37 |
| Regional constraint | o/e 1.23 | unconstrained · MANE · 32 kb · p 4.7e-50 · regional, not allelic |
| Overall | ||
| CADD | 0.021 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 1.09% | 92 |
| East Asiangrpmax | 1.02% | 98 |
| South Asian | 0.987% | 101 |
| Finnishnot grpmax-eligible | 0.98% | 102 |
| Remaining individualsnot grpmax-eligible | 0.958% | 104 |
| European (non-Finnish) | 0.918% | 109 |
| Admixed American | 0.567% | 176 |
| African / African-American | 0.485% | 206 |
| Middle Eastern | 0.233% | 429 |
| Amishnot grpmax-eligible | 0.229% | 437 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Cys1872Ser
- Coding
- c.5614T>A
- MANE Select
- NM_138420
- dbSNP
- rs181708085
- Type
- single nucleotide variant
- Location
- chr14:104949837 (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-cys1872ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown