Is AKAP10 p.Val341Phe (c.1021G>T) pathogenic?

AKAP10 p.Val341Phe (c.1021G>T) is classified Uncertain significance in AKAP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-22). AlphaMissense: likely benign (0.2451); Very rare (popmax 0.00017%, nfe).

How common is AKAP10 p.Val341Phe (c.1021G>T) in the general population?

AKAP10 p.Val341Phe (c.1021G>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about AKAP10 p.Val341Phe (c.1021G>T)?

AlphaMissense predicts likely benign (score 0.2451) — an in-silico prediction, not a clinical call.

AKAP10 p.Val341Phe

c.1021G>T · VCV4030988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2451 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2451	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -3.2, phastCons 0.003
Regional constraint	o/e 0.83	unconstrained · MANE · 71 kb · p 2e-06 · regional, not allelic
Overall
CADD	21.1	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 0.00017% European (non-Finnish) · 2/1,178,356 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,458,206 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.Val341Phe
Coding: c.1021G>T
MANE Select: NM_007202
Type: single nucleotide variant
Location: chr17:19941866 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.23 · 2 PDB
Residue 341: the rgs 1 domain

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

Similar variants

AKAP10 p.Val341Ile Uncertain significance ★ ⚠ same residue
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

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-val341phe (accessed [today's date]).

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