Is AHNAK2 p.Ala3948Val (c.11843C>T) pathogenic?

AHNAK2 p.Ala3948Val (c.11843C>T) is classified Uncertain significance in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0957); Ultra-rare (popmax 0.0331%, mid).

How common is AHNAK2 p.Ala3948Val (c.11843C>T) in the general population?

AHNAK2 p.Ala3948Val (c.11843C>T) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

What do computational predictors say about AHNAK2 p.Ala3948Val (c.11843C>T)?

AlphaMissense predicts likely benign (score 0.0957) — an in-silico prediction, not a clinical call.

AHNAK2 p.Ala3948Val

c.11843C>T · rs763788686 · VCV2391421

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0957 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0957	likely benign
REVEL	0.034	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 -0.98	GERP -0.4
Regional constraint	o/e 1.21	unconstrained · MANE · 5,079 bp · p 5.5e-23 · regional, not allelic
Overall
CADD	0.021	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 0.0331% Middle Eastern · 2/6,048 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.0018% 29/1,611,280 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,024
East Asian	0.00448%	22,297
African / African-American	0.0027%	37,027
European (non-Finnish)	0.0017%	58,953
Admixed American	0.00167%	59,788
Remaining individualsnot grpmax-eligible	0.0016%	62,428
South Asian	0.0011%	90,934

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.Ala3948Val
Coding: c.11843C>T
MANE Select: NM_138420
dbSNP: rs763788686
Type: single nucleotide variant
Location: chr14:104943608 (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-ala3948val (accessed [today's date]).

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