Is AKAP1 p.Val60Met (c.178G>A) pathogenic?

AKAP1 p.Val60Met (c.178G>A) is classified Benign in AKAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-31). AlphaMissense: likely benign (0.0768); Common (popmax 8.33%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about AKAP1 p.Val60Met (c.178G>A)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

AKAP1 p.Val60Met

Q: How common is AKAP1 p.Val60Met (c.178G>A) in the general population?

AKAP1 p.Val60Met (c.178G>A) is common (popmax 8.33%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.178G>A · rs2230770 · VCV789843

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.33%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -8.29	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 -0.84	GERP -3.5
Regional constraint	o/e 0.73	unconstrained · MANE · 353 bp · p 0.0011 · regional, not allelic
Overall
CADD	0.032	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 8.33% African / African-American · 6,244/74,968 alleles

Filtering AF 8.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.09%

Overall 0.449% 7,241/1,614,038 alleles · common exomes 3,618/1,461,870 · genomes 3,623/152,168 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.33%	12
Remaining individualsnot grpmax-eligible	0.629%	159
Admixed American	0.558%	179
Middle Eastern	0.313%	319
Ashkenazi Jewishnot grpmax-eligible	0.135%	740
South Asian	0.0253%	3,960
European (non-Finnish)	0.0156%	6,413
East Asian	0.00668%	14,959

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: AKAP1
Protein: p.Val60Met
Coding: c.178G>A
MANE Select: NM_003488
dbSNP: rs2230770
Type: single nucleotide variant
Location: chr17:57105642 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.67 (gnomAD)
Structure: AlphaFold pLDDT 57.02
Residue 60: a UniProt-annotated variant site (in)

Full AKAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AKAP1 c.1976-6A>G Benign ★★ same type
AKAP1 p.Ala218Thr Benign ★★ same type
AKAP1 p.Gly323Ser Benign ★★ same type
AKAP1 p.Pro475= Benign ★★ same type
AKAP1 p.Pro818= Benign ★★ same type
AKAP1 p.Ser330Gly Benign ★★ same type
AKAP1 p.Ser388= Benign ★★ same type
AKAP1 p.Thr521Ile 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/akap1-p-val60met (accessed [today's date]).

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