Is AHNAK2 p.Arg628Pro (c.1883G>C) pathogenic?

AHNAK2 p.Arg628Pro (c.1883G>C) is classified Uncertain significance in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). AlphaMissense: likely benign (0.1834); Very rare (popmax 0.00167%, amr).

How common is AHNAK2 p.Arg628Pro (c.1883G>C) in the general population?

AHNAK2 p.Arg628Pro (c.1883G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AHNAK2 p.Arg628Pro (c.1883G>C)?

AlphaMissense predicts likely benign (score 0.1834) — an in-silico prediction, not a clinical call.

AHNAK2 p.Arg628Pro

c.1883G>C · rs772922301 · VCV3100732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1834	likely benign
REVEL	0.045	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -2.2, phastCons 0.001
Regional constraint	o/e 1.23	unconstrained · MANE · 32 kb · p 4.7e-50 · regional, not allelic
Overall
CADD	0.073	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000744% 12/1,613,822 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,466
African / African-American	0.00134%	74,904
European (non-Finnish)	0.000763%	131,099

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.Arg628Pro
Coding: c.1883G>C
MANE Select: NM_138420
dbSNP: rs772922301
Type: single nucleotide variant
Location: chr14:104953568 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Residue 628: the 'disordered' region

Full AHNAK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AHNAK2 p.Arg628Cys Uncertain significance ★ ⚠ same residue
AHNAK2 p.Arg628Leu 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

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-arg628pro (accessed [today's date]).

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