Is AHNAK2 p.Asp1815Glu (c.5445T>G) pathogenic?

AHNAK2 p.Asp1815Glu (c.5445T>G) is classified Benign in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). AlphaMissense: likely benign (0.1952); Rare (popmax 0.707%, afr).

How common is AHNAK2 p.Asp1815Glu (c.5445T>G) in the general population?

AHNAK2 p.Asp1815Glu (c.5445T>G) is rare (popmax 0.707%, afr) (gnomAD).

What do computational predictors say about AHNAK2 p.Asp1815Glu (c.5445T>G)?

AlphaMissense predicts likely benign (score 0.1952) — an in-silico prediction, not a clinical call.

AHNAK2 p.Asp1815Glu

c.5445T>G · rs140200392 · VCV2644796

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1952 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.707%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1952	likely benign
REVEL	0.037	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 -1.2
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 0.707% African / African-American · 471/66,654 alleles

Filtering AF 0.654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.633%

Overall 0.036% 563/1,562,146 alleles · rare exomes 294/1,430,204 · genomes 269/131,942 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.707%	142
Remaining individualsnot grpmax-eligible	0.0411%	2,431
Admixed American	0.0399%	2,507
Middle Eastern	0.0338%	2,960
South Asian	0.0124%	8,049
East Asian	0.0118%	8,462
European (non-Finnish)	0.00226%	44,308
Finnishnot grpmax-eligible	0.00163%	61,364

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.Asp1815Glu
Coding: c.5445T>G
MANE Select: NM_138420
dbSNP: rs140200392
Type: single nucleotide variant
Location: chr14:104950006 (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.Asp1815Ala 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-asp1815glu (accessed [today's date]).

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