Is AKAP6 p.Arg1069Ser (c.3205C>A) pathogenic?

AKAP6 p.Arg1069Ser (c.3205C>A) is classified Uncertain significance in AKAP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). AlphaMissense: ambiguous (0.3863); Absent from gnomAD v4.1.

How common is AKAP6 p.Arg1069Ser (c.3205C>A) in the general population?

AKAP6 p.Arg1069Ser (c.3205C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AKAP6 p.Arg1069Ser (c.3205C>A)?

AlphaMissense predicts ambiguous (score 0.3863) — an in-silico prediction, not a clinical call.

AKAP6 p.Arg1069Ser

c.3205C>A · VCV4032727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3863 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3863	ambiguous
REVEL	0.23	benign-leaning
SaProt	LLR -4.77	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 3.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 279 kb · p 0.34 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AKAP6
Protein: p.Arg1069Ser
Coding: c.3205C>A
MANE Select: NM_004274
Type: single nucleotide variant
Location: chr14:32735715 (GRCh38)
Gene constraint: LOEUF 0.367 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 43.07

Full AKAP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AKAP6 p.Arg1069Cys Uncertain significance ★ ⚠ same residue
AKAP6 p.Arg1069His Uncertain significance ★ ⚠ same residue
AKAP6 p.Asn558Asp Benign ★★ same type
AKAP6 p.Glu2168= Benign ★★ same type
AKAP6 p.Glu892Lys Benign ★★ same type
AKAP6 p.Thr1516Ala Benign ★★ same type
AKAP6 p.Ala1022Val Uncertain significance ★ ⚠ same type
AKAP6 p.Ala123Asp Uncertain significance ★ ⚠ 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/akap6-p-arg1069ser (accessed [today's date]).

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