Is AHNAK2 p.Ala617fs (c.1849del) pathogenic?

AHNAK2 p.Ala617fs (c.1849del) is classified Uncertain significance in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-01). Very rare (popmax 0.000424%, nfe).

How common is AHNAK2 p.Ala617fs (c.1849del) in the general population?

AHNAK2 p.Ala617fs (c.1849del) is very rare (popmax 0.000424%, nfe) (gnomAD).

AHNAK2 p.Ala617fs

c.1849del · rs1205572179 · VCV493154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.9	GERP -2
Overall
CADD	12.53	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,878 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,744 alleles · very rare exomes 4/1,461,694 · genomes 1/152,050 · joint denominator

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.Ala617fs
Coding: c.1849del
MANE Select: NM_138420
dbSNP: rs1205572179
Type: Deletion
Location: chr14:104953602 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Residue 617: the 'disordered' region

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

Similar variants

AHNAK2 p.Asp3465fs Uncertain significance ★ same type
AHNAK2 p.3472KFKMP[1] Likely benign ★ same type
AHNAK2 p.Ala1284fs Likely benign ★ same type
AHNAK2 p.Glu3560_Val3569del Benign ★ same type
AHNAK2 p.Leu2086_Asp2092del Likely benign ★ same type
AHNAK2 p.Pro2126fs 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-ala617fs (accessed [today's date]).

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