Is AHNAK2 p.Ala2015Glu (c.6044C>A) pathogenic?

AHNAK2 p.Ala2015Glu (c.6044C>A) is classified Benign in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). AlphaMissense: likely benign (0.1959); Rare (popmax 0.131%, afr).

How common is AHNAK2 p.Ala2015Glu (c.6044C>A) in the general population?

AHNAK2 p.Ala2015Glu (c.6044C>A) is rare (popmax 0.131%, afr) (gnomAD).

What do computational predictors say about AHNAK2 p.Ala2015Glu (c.6044C>A)?

AlphaMissense predicts likely benign (score 0.1959) — an in-silico prediction, not a clinical call.

AHNAK2 p.Ala2015Glu

c.6044C>A · rs748398097 · VCV2644762

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1959 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.131%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1959	likely benign
REVEL	0.118	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 -14	GERP -1.1
Regional constraint	o/e 1.23	unconstrained · MANE · 32 kb · p 4.7e-50 · regional, not allelic
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.131% African / African-American · 96/73,290 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00903% 143/1,583,486 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.131%	763
Middle Eastern	0.116%	861
Remaining individualsnot grpmax-eligible	0.0228%	4,392
Admixed American	0.00527%	18,973
European (non-Finnish)	0.00198%	50,436

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.Ala2015Glu
Coding: c.6044C>A
MANE Select: NM_138420
dbSNP: rs748398097
Type: single nucleotide variant
Location: chr14:104949407 (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.Ala2015= Benign ★ 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-ala2015glu (accessed [today's date]).

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