Is AHNAK2 p.Ala813Val (c.2438C>T) pathogenic?

AHNAK2 p.Ala813Val (c.2438C>T) is classified Likely benign in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.1044); Ultra-rare (popmax 0.0148%, afr).

How common is AHNAK2 p.Ala813Val (c.2438C>T) in the general population?

AHNAK2 p.Ala813Val (c.2438C>T) is ultra-rare (popmax 0.0148%, afr) (gnomAD).

What do computational predictors say about AHNAK2 p.Ala813Val (c.2438C>T)?

AlphaMissense predicts likely benign (score 0.1044) — an in-silico prediction, not a clinical call.

AHNAK2 p.Ala813Val

c.2438C>T · VCV4639280

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1044 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1044	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 -0.92
Regional constraint	o/e 1.23	unconstrained · MANE · 32 kb · p 4.7e-50 · regional, not allelic
Overall
CADD	0.439	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 0.0148% African / African-American · 11/74,328 alleles

Filtering AF 0.00822% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00638%

Overall 0.00205% 33/1,612,672 alleles · ultra-rare exomes 26/1,461,436 · genomes 7/151,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0148%	6,757
South Asian	0.00329%	30,349
Remaining individualsnot grpmax-eligible	0.0032%	31,208
East Asian	0.00223%	44,762
European (non-Finnish)	0.00136%	73,729

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.Ala813Val
Coding: c.2438C>T
MANE Select: NM_138420
Type: single nucleotide variant
Location: chr14:104953013 (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.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
AHNAK2 p.Ala1818Thr Benign/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-ala813val (accessed [today's date]).

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