Is AKAP10 p.Phe25Ser (c.74T>C) pathogenic?

AKAP10 p.Phe25Ser (c.74T>C) is classified Uncertain significance in AKAP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely pathogenic (0.9434); Very rare (popmax 0.00081%, nfe).

How common is AKAP10 p.Phe25Ser (c.74T>C) in the general population?

AKAP10 p.Phe25Ser (c.74T>C) is very rare (popmax 0.00081%, nfe) (gnomAD).

What do computational predictors say about AKAP10 p.Phe25Ser (c.74T>C)?

AlphaMissense predicts likely pathogenic (score 0.9434) — an in-silico prediction, not a clinical call.

AKAP10 p.Phe25Ser

c.74T>C · VCV3513763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9434 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00081%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9434	likely pathogenic
REVEL	0.178	moderately benign-leaning
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 71 kb · p 2e-06 · regional, not allelic
Overall
CADD	25.6	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

Grpmax group 0.00081% European (non-Finnish) · 8/987,960 alleles

Filtering AF 0.000348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000252%

Overall 0.000739% 8/1,082,642 alleles · very rare

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: AKAP10
Protein: p.Phe25Ser
Coding: c.74T>C
MANE Select: NM_007202
Type: single nucleotide variant
Location: chr17:19977606 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.23 · 2 PDB
Residue 25: the 'disordered' region

Full AKAP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AKAP10 c.1467+5C>A Uncertain significance ★ same type
AKAP10 p.Ala196Val Uncertain significance ★ ⚠ same type
AKAP10 p.Ala274Thr Uncertain significance ★ ⚠ same type
AKAP10 p.Ala274Val Uncertain significance ★ ⚠ same type
AKAP10 p.Ala280Thr Uncertain significance ★ ⚠ same type
AKAP10 p.Ala326Gly Uncertain significance ★ ⚠ same type
AKAP10 p.Ala564Val Uncertain significance ★ ⚠ same type
AKAP10 p.Ala569Val 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/akap10-p-phe25ser (accessed [today's date]).

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