Is AHNAK2 p.Asp2012Glu (c.6036T>A) pathogenic?

AHNAK2 p.Asp2012Glu (c.6036T>A) is classified Benign in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1464); Rare (popmax 0.427%, nfe).

How common is AHNAK2 p.Asp2012Glu (c.6036T>A) in the general population?

AHNAK2 p.Asp2012Glu (c.6036T>A) is rare (popmax 0.427%, nfe) (gnomAD).

What do computational predictors say about AHNAK2 p.Asp2012Glu (c.6036T>A)?

AlphaMissense predicts likely benign (score 0.1464) — an in-silico prediction, not a clinical call.

AHNAK2 p.Asp2012Glu

c.6036T>A · rs200936018 · VCV2644763

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1464 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.427%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1464	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 -1.1
Regional constraint	o/e 1.23	unconstrained · MANE · 32 kb · p 4.7e-50 · regional, not allelic
Overall
CADD	0.007	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 0.427% European (non-Finnish) · 4,960/1,161,722 alleles

Filtering AF 0.417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.413%

Overall 0.352% 5,586/1,586,356 alleles · rare exomes 5,226/1,441,220 · genomes 360/145,136 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.427%	234
Remaining individualsnot grpmax-eligible	0.343%	292
South Asian	0.24%	416
Admixed American	0.223%	448
Middle Eastern	0.133%	754
African / African-American	0.0503%	1,986
Finnishnot grpmax-eligible	0.0259%	3,859
East Asian	0.0179%	5,584
Ashkenazi Jewishnot grpmax-eligible	0.00687%	14,556

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.Asp2012Glu
Coding: c.6036T>A
MANE Select: NM_138420
dbSNP: rs200936018
Type: single nucleotide variant
Location: chr14:104949415 (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.Asp2012His 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-asp2012glu (accessed [today's date]).

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