Is AHNAK2 p.Ser4485Pro (c.13453T>C) pathogenic?

AHNAK2 p.Ser4485Pro (c.13453T>C) is classified Benign in AHNAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-01). AlphaMissense: likely benign (0.1213); Low-frequency (popmax 1.52%, eas).

How common is AHNAK2 p.Ser4485Pro (c.13453T>C) in the general population?

AHNAK2 p.Ser4485Pro (c.13453T>C) is low-frequency (popmax 1.52%, eas) (gnomAD).

What do computational predictors say about AHNAK2 p.Ser4485Pro (c.13453T>C)?

AlphaMissense predicts likely benign (score 0.1213) — an in-silico prediction, not a clinical call.

AHNAK2 p.Ser4485Pro

c.13453T>C · rs150385420 · VCV3025793

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1213 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.52%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1213	likely benign
REVEL	0.046	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 -1.9	GERP -1.1
Regional constraint	o/e 1.21	unconstrained · MANE · 5,079 bp · p 5.5e-23 · regional, not allelic
Overall
CADD	16.04	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 1.52% East Asian · 682/44,834 alleles

Filtering AF 1.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.39%

Overall 0.0455% 734/1,613,462 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.52%	66
Remaining individualsnot grpmax-eligible	0.0288%	3,470
South Asian	0.00659%	15,176
Admixed American	0.00333%	29,986
European (non-Finnish)	0.0022%	45,374

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.Ser4485Pro
Coding: c.13453T>C
MANE Select: NM_138420
dbSNP: rs150385420
Type: single nucleotide variant
Location: chr14:104941998 (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.Ser4485Leu 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-ser4485pro (accessed [today's date]).

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