Is AKAP6 p.Ser929Pro (c.2785T>C) pathogenic?

AKAP6 p.Ser929Pro (c.2785T>C) is classified Uncertain significance in AKAP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely pathogenic (0.9822); Absent from gnomAD v4.1.

How common is AKAP6 p.Ser929Pro (c.2785T>C) in the general population?

AKAP6 p.Ser929Pro (c.2785T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AKAP6 p.Ser929Pro (c.2785T>C)?

AlphaMissense predicts likely pathogenic (score 0.9822) — an in-silico prediction, not a clinical call.

AKAP6 p.Ser929Pro

c.2785T>C · VCV3848589

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9822 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9822	likely pathogenic · top 3% in AKAP6
REVEL	0.202	benign-leaning
SaProt	LLR -11.55	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 3.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 279 kb · p 0.34 · regional, not allelic
Overall
CADD	27.6	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.Ser929Pro
Coding: c.2785T>C
MANE Select: NM_004274
Type: single nucleotide variant
Location: chr14:32678365 (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.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
AKAP6 p.Ala146Thr Uncertain significance ★ ⚠ same type
AKAP6 p.Ala1716Ser 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-ser929pro (accessed [today's date]).

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