Is AKAP6 p.Ala172Thr (c.514G>A) pathogenic?

AKAP6 p.Ala172Thr (c.514G>A) is classified Uncertain significance in AKAP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). AlphaMissense: likely benign (0.085); Ultra-rare (popmax 0.0495%, mid).

How common is AKAP6 p.Ala172Thr (c.514G>A) in the general population?

AKAP6 p.Ala172Thr (c.514G>A) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about AKAP6 p.Ala172Thr (c.514G>A)?

AlphaMissense predicts likely benign (score 0.085) — an in-silico prediction, not a clinical call.

AKAP6 p.Ala172Thr

c.514G>A · rs201978712 · VCV2363323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.085 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.085	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -5.92	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 8.6	GERP 6.2, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 112 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	27.3	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 0.0495% Middle Eastern · 3/6,060 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00384% 62/1,614,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,020
East Asian	0.0267%	3,740
Admixed American	0.0133%	7,504
South Asian	0.00329%	30,361
European (non-Finnish)	0.00297%	33,714
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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: AKAP6
Protein: p.Ala172Thr
Coding: c.514G>A
MANE Select: NM_004274
dbSNP: rs201978712
Type: single nucleotide variant
Location: chr14:32535743 (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-ala172thr (accessed [today's date]).

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