Is AHNAK2 p.Asp2475Glu (c.7425T>G) pathogenic?

AHNAK2 p.Asp2475Glu (c.7425T>G) is classified Uncertain significance in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.1605); Ultra-rare (popmax 0.0596%, afr).

How common is AHNAK2 p.Asp2475Glu (c.7425T>G) in the general population?

AHNAK2 p.Asp2475Glu (c.7425T>G) is ultra-rare (popmax 0.0596%, afr) (gnomAD).

What do computational predictors say about AHNAK2 p.Asp2475Glu (c.7425T>G)?

AlphaMissense predicts likely benign (score 0.1605) — an in-silico prediction, not a clinical call.

AHNAK2 p.Asp2475Glu

c.7425T>G · rs376195156 · VCV2360283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1605 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0596%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1605	likely benign
REVEL	0.112	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 -0.63
Regional constraint	o/e 1.23	unconstrained · MANE · 32 kb · p 4.7e-50 · regional, not allelic
Overall
CADD	0.009	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 0.0596% African / African-American · 44/73,874 alleles

Filtering AF 0.0456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0406%

Overall 0.0036% 58/1,611,562 alleles · ultra-rare exomes 37/1,461,240 · genomes 21/150,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0596%	1,679
Remaining individualsnot grpmax-eligible	0.00962%	10,399
Admixed American	0.00669%	14,956
East Asian	0.00224%	44,718
European (non-Finnish)	0.000254%	393,113

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.Asp2475Glu
Coding: c.7425T>G
MANE Select: NM_138420
dbSNP: rs376195156
Type: single nucleotide variant
Location: chr14:104948026 (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.Asp2475Ala Uncertain significance ★ ⚠ 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-asp2475glu (accessed [today's date]).

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