Is AHNAK2 p.Ala3280Asp (c.9839C>A) pathogenic?

AHNAK2 p.Ala3280Asp (c.9839C>A) is classified Uncertain significance in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely benign (0.2827); Ultra-rare (popmax 0.0963%, eas).

How common is AHNAK2 p.Ala3280Asp (c.9839C>A) in the general population?

AHNAK2 p.Ala3280Asp (c.9839C>A) is ultra-rare (popmax 0.0963%, eas) (gnomAD).

What do computational predictors say about AHNAK2 p.Ala3280Asp (c.9839C>A)?

AlphaMissense predicts likely benign (score 0.2827) — an in-silico prediction, not a clinical call.

AHNAK2 p.Ala3280Asp

c.9839C>A · rs191490316 · VCV2352911

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2827 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0963%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.2827	likely benign
REVEL	0.099	moderately 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 -20	GERP -0.75
Regional constraint	o/e 1.21	unconstrained · MANE · 5,079 bp · p 5.5e-23 · regional, not allelic
Overall
CADD	15.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0963% East Asian · 43/44,652 alleles

Filtering AF 0.0734% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0654%

Overall 0.0062% 99/1,596,866 alleles · ultra-rare exomes 83/1,458,350 · genomes 16/138,516 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0963%	1,038
Remaining individualsnot grpmax-eligible	0.00806%	12,409
Finnishnot grpmax-eligible	0.00635%	15,743
South Asian	0.00554%	18,040
European (non-Finnish)	0.00351%	28,510
Admixed American	0.0017%	58,864

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.Ala3280Asp
Coding: c.9839C>A
MANE Select: NM_138420
dbSNP: rs191490316
Type: single nucleotide variant
Location: chr14:104945612 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)

Full AHNAK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-ala3280asp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown